Novel prostate cancer genes

ABSTRACT

The present invention relates to all facets of novel polynucleotides, the polypeptides they encode, antibodies and specific binding partners thereto, and their applications to research, diagnosis, drug discovery, therapy, clinical medicine, forensic science and medicine, etc. The polynucleotides are differentially-regulated in prostate cancer and are therefore useful in variety of ways, including, but not limited to, as molecular markers, as drug targets, and for detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, determining predisposition to, etc., diseases and conditions, to prostate cancer.

DESCRIPTION OF THE DRAWINGS

[0001] FIGS. 1-7 show amino acid sequence alignments betweenpolypeptides of the present invention, and polypeptides listed in publicdatabases. SEQ ID NOS for the polypeptides of the present invention arelisted in Table 1. Others are as follows: KIAA0534 (SEQ ID NO 32);KIAA1217 (SEQ ID NO 33); KIAA0301 (SEQ ID NO 34): AF441770 (SEQ ID NO35); XM_(—)085817 (SEQ ID NO 36); AK001276 (SEQ ID NO 37); XM_(—)033473(SEQ ID NO 38); AK022207 (SEQ ID NO 39).

[0002]FIG. 8 shows differential display patterns for genes of thepresent invention. The white arrowhead indicates the position of a DNAfragment derived from a differentially regulated gene of the presentinvention. The experiments were performed in duplicate. Each sample set(4 lanes) contains a duplicate from normal (left) prostate tissue and aduplicate tumor (right) prostate tissue from the same individual. Thereare several sample sets for each gene.

DESCRIPTION OF THE INVENTION

[0003] The present invention relates to all facets of novelpolynucleotides, the polypeptides they encode, antibodies and specificbinding partners thereto, and their applications to research, diagnosis,drug discovery, therapy, clinical medicine, forensic science andmedicine, etc. The polynucleotides are differentially regulated inprostate cancer and are therefore useful in variety of ways, including,but not limited to, as molecular markers, as drug targets, and fordetecting, diagnosing, staging, monitoring, prognosticating, preventingor treating, determining predisposition to, etc., diseases andconditions, such as cancer, especially relating to prostate. Theidentification of specific genes, and groups of genes, expressed inpathways physiologically relevant to prostate permits the definition offunctional and disease pathways, and the delineation of targets in thesepathways which are useful in diagnostic, therapeutic, and clinicalapplications. The present invention also relates to methods of using thepolynucleotides and related products (proteins, antibodies, etc.) inbusiness and computer-related methods, e.g., advertising, displaying,offering, selling, etc., such products for sale, commercial use,licensing, etc.

DESCRIPTION OF THE DRAWINGS

[0004] FIGS. 1-7 show amino acid sequence alignments betweenpolypeptides of the present invention, and polypeptides listed in publicdatabases. SEQ ID NOS for the polypeptides of the present invention arelisted in Table 1. Others are as follows: KIAA0534 (SEQ ID NO 32);KIAA1217 (SEQ ID NO 33); KIAA0301 (SEQ ID NO 34): AF441770 (SEQ ID NO35); XM_(—)085817 (SEQ ID NO 36); AK001276 (SEQ ID NO 37); XM_(—)033473(SEQ ID NO 38); AK022207 (SEQ ID NO 39).

[0005]FIG. 8 shows differential display patterns for genes of thepresent invention. The white arrowhead indicates the position of a DNAfragment derived from a differentially regulated gene of the presentinvention. The experiments were performed in duplicate. Each sample set(4 lanes) contains a duplicate from normal (left) prostate tissue and aduplicate tumor (right) prostate tissue from the same individual. Thereare several sample sets for each gene.

DESCRIPTION OF THE INVENTION

[0006] The present invention relates to all facets of novelpolynucleotides, the polypeptides they encode, antibodies and specificbinding partners thereto, and their applications to research, diagnosis,drug discovery, therapy, clinical medicine, forensic science andmedicine, etc. The polynucleotides are differentially regulated inprostate cancer and are therefore useful in variety of ways, including,but not limited to, as molecular markers, as drug targets, and fordetecting, diagnosing, staging, monitoring, prognosticating, preventingor treating, determining predisposition to, etc., diseases andconditions, such as cancer, especially relating to prostate. Theidentification of specific genes, and groups of genes, expressed inpathways physiologically relevant to prostate permits the definition offunctional and disease pathways, and the delineation of targets in thesepathways which are useful in diagnostic, therapeutic, and clinicalapplications. The present invention also relates to methods of using thepolynucleotides and related products (proteins, antibodies, etc.) inbusiness and computer-related methods, e.g., advertising, displaying,offering, selling, etc., such products for sale, commercial use,licensing, etc.

[0007] Prostate cancer is the most common form of cancer diagnosed inthe American male, occurring predominantly in males over age 50. Thenumber of men diagnosed with prostate cancer has steadily increased as aresult of the increasing population of older men. In the US,approximately 198,000 men were diagnosed with prostate cancer in 2001,and an estimated 31,500 men in the US died from the disease. Incomparison, 1998 estimates for lung cancer in men were 171,500 cases and160,100 deaths, and for colorectal cancer, the estimates were 131,600cases and 56,000 deaths. Despite these high numbers, 89 percent of mendiagnosed with the disease will survive at least five years and 63percent will survive at least 10 years.

[0008] Patients having prostate cancer display a wide range ofphenotypes. In some men, following detection, the tumor remains a latenthistological tumor and does not become clinically significant. However,in other men, the tumor progresses rapidly, metastasizing and killingthe patient in a relatively short time. Prostate cancer can be cured ifthe tumor is confined to a small region of the gland and is discoveredat early stage. In such cases, radiation or surgical removal oftenresults in complete elimination of the disease. Frequently, however, theprostate cancer has already spread to surrounding tissue andmetastasized to remote locations. In these cases, radiation and othertherapies, are less likely to effect a complete cure.

[0009] Androgen deprivation is a conventional therapy to treat prostatecancer. Androgen blockade can be achieved through several differentroutes. Androgen suppressive drugs include, e.g., Lupron (leuprolideacetate), Casodex (bicalutamide), Eulexin (flutamide), Nilandron(nilutamide), Zoladex (goserelin acetate implant), and Viadur(leuprolide acetate), which act through several different mechanisms.While these drugs may offer remission and tumor regression in manycases, often the therapeutic effects are only temporary. Prostate tumorslose their sensitivity to such treatments, and becomeandrogen-independent. Thus, new therapies are clearly needed.

[0010] The first clinical symptoms of prostate cancer are typicallyurinary disturbances, including painful and more frequent urination.Diagnosis for prostate cancer is usually accomplished using acombination of different procedures. Since the prostate is located nextto the rectum, rectal digital examination allows the prostate to beexamined manually for the presence of hyperplasia and abnormal tissuemasses. Usually, this is the first line of detection. If a palpable massis observed, a blood specimen can be assayed for prostate-specificantigen (PSA). Very little PSA is present in the blood of a healthyindividual, but BPH and prostate cancer can cause large amounts of PSAto be released into the blood, indicating the presence of diseasedtissue. Definitive diagnosis is generally accomplished by biopsy of theprostate tissue.

[0011] No single gene or protein has been identified which isresponsible for the etiology of all prostate cancers. Although PSA iswidely used as a diagnostic reagent, it has limitations in itssensitivity and its ability to detect early cancers. It is estimatedthat approximately 20% to 30% of tumors will be missed when PSA is usedalone. It is likely that diagnostic and prognostic markers for prostatecancer disease will involve the identification and use of many differentgenes and gene products to reflect its multifactorial origin.

[0012] A continuing goal is to characterize the gene expression patternsof the various prostate cancers to genetically differentiate them,providing important guidance in preventing and treating cancers.Molecular pictures of cancer, such as the pattern ofdifferentially-regulated genes identified herein, provide an importanttool for molecularly dissecting and classifying cancer, identifying drugtargets, providing prognosis and therapeutic information, etc. Forinstance, an array of polynucleotides corresponding to genesdifferentially regulated in prostate cancer can be used to screen tissuesamples for the existence of cancer, to categorize the cancer (e.g., bythe particular pattern observed), to grade the cancer (e.g., by thenumber of differentially-regulated genes and their amounts ofexpression), to identify the source of a secondary tumor, to screen formetastatic cells, etc. These arrays can be used in combination withother markers, e.g., PSA, PMSA (prostate membrane specific antigen), orany of the grading systems used in clinical medicine.

[0013] As indicated by these studies, cancer is a highly diversedisease. Although all cancers share certain characteristics, theunderlying cause and disease progression can differ significantly frompatient to patient. So far, over a dozen distinct genes have beenidentified which, when mutant, result in a cancer. In prostate cancer,alone, a handful of different genes have been isolated which eithercause the cancer, or produce a predisposition to it. As a consequence,disease phenotypes for a particular cancer do not look all the same. Inaddition to the differences in the gene(s) responsible for the cancer,heterogeneity among individuals, e.g., in age, health, sex, and geneticbackground, can also influence the disease and its progression. Genepenetrance, in particular, can vary widely among population members.Recent studies have shown tremendous diversity in gene expressionpatterns among cancer patients. For these and other reasons, onegene/polypeptide target alone can be insufficient to diagnose or treat acancer. Even a gene which is highly differentially-expressed andpenetrant in cancer patients may not be so highly expressed in allpatients and at all stages of the cancer. By selecting a set of genesand/or the polypeptides they encode, cancer diagnostics and therapeuticscan be designed which effectively diagnose and treat a population ofdiseased individuals, rather than only a small handful when single genesare targeted.

[0014] Table 1 is a list of the genes, and their correspondingfunctional and structural polypeptide domains.

[0015] Membrane (i.e., cell-surface) proteins coded for by up-regulatedgenes (e.g., PCP0816) are useful targets for antibodies and otherbinding partners (e.g., ligands, aptamers, small peptides, etc.) toselectively target agents to a prostate cancer tissue for any purpose,included, but not limited to, imaging, therapeutic, diagnostic, drugdelivery, gene therapy, etc. For example, binding partners, such asantibodies, can be used to treat carcinomas in analogy to how c-erbB-2antibodies are used to breast cancer. Membrane (e.g., PCP405) when shedinto the blood and other fluid) and secretable proteins (e.g., PCP0664)can also be used as diagnostic markers for cancer, and to assess theprogress of the disease, e.g., in analogy to how PSA levels are used todiagnose prostate cancer. Useful antibodies or other binding partnersinclude those that are specific for parts of the polypeptide which areexposed extracellularly as indicated in Table 1. Table 1 also summarizesthe expression profile of these genes.

[0016] Polynucleotides of the present invention can also be used todetect metastatic cells in the blood. For instance, Pcp405, Pc0177,Pcp0677, and Pcp0806 are absent from peripheral blood cells, and cantherefore be used in diagnostic tests to assess whether cancer cellshave metastasized from the primary site.

[0017] Polynucleotides of the present invention have been mapped tospecific chromosomal bands. Different human disorders are associatedwith these chromosome locations. See, Table 2. The polynucleotides andpolypeptides they encode can be used as linkage markers, diagnostictargets, therapeutic targets, for any of the mentioned disorders, aswell as any disorders or genes mapping in proximity to them. Ofparticular interest are those genes which map to cancer loci, such asPcp0405, Pcp0459, Pcp0677, and Pcp0762.

[0018] The present invention relates to the complete polynucleotide andpolypeptide sequences disclosed herein, as well as fragments thereof.Useful fragments include those which are unique and which do not overlapany known gene, which overlap with a known sequence, which spanalternative splice junctions, which are unique to a public sequence asindicated in the Figures, which span an alternative splice junction of apublic sequence, etc. Unique sequences can also be described as beingspecific for a gene because they are characteristic of the gene, but notrelated genes.

[0019] Below, for illustration, are some examples of polypeptides(included are the polynucleotides which encode them); however, thepresent invention includes all fragments, especially of the categoriesmentioned above are exemplified below.

[0020] PCP405 (SEQ ID NO 1-2): polypeptides comprising, consisting of,or consisting essentially of about amino acids 1-351, 941, polypeptidefragments thereof, and polynucleotides encoding said polypeptides.PCP405 has high expression in the adrenal gland, brain and pituitarygland, and codes for a polypeptide which comprises domainscharacteristic of the attractins and other cell adhesion and guidanceproteins. See, e.g., Duke-Cohan et al., Proc. Natl. Acad. Sci.,95:11336-11341, 1998.

[0021] PC0177A (SEQ ID NOS 10-11): polypeptides comprising, consistingof, or consisting essentially of about amino acids 1-85, 560-594,1139-1167, 1167-1168, 1168-1744, polypeptide fragments thereof, andpolynucleotides encoding said polypeptides; PC0177B (SEQ ID NOS 12-13):polypeptides comprising, consisting of, or consisting essentially ofabout amino acids 1-85, 559-560, 1104-1132, 1132-1133, 1132-1709,polypeptide fragments thereof, and polynucleotides encoding saidpolypeptides; PC0177C (SEQ ID NOS 14-15): polypeptides comprising,consisting of, or consisting essentially of about amino acids 1-85,559-560, 1104-1132, 1703-1908, polypeptide fragments thereof, andpolynucleotides encoding said polypeptides; PC0177D (SEQ ID NOS 16-17):polypeptides comprising, consisting of, or consisting essentially ofabout amino acids 1-85, 559-560, polypeptide fragments thereof, andpolynucleotides encoding said polypeptides. PC0177 comprise coil-coildomains involved in protein interactions.

[0022] PCP454A (SEQ ID NO 6-7; FIG. 3): polypeptides comprising,consisting of, or consisting essentially of about amino acids 1-1890,polypeptide fragments thereof, and polynucleotides encoding saidpolypeptides. PCP454B (SEQ ID NOS 4-5) codes for a 577-amino acidpolypeptide. This polypeptide comprises a nucleotide binding site whichcan be used to assay for its activity, e.g., by a filtration-type assayusing radioactive ATP or other nucleotides. Nucleotide binding can alsobe used to purify the polypeptide, e.g., using a column comprising anucleotide. PCP454A and B are contiguous, and a transcript has also beendetected (SEQ ID NO 3) which comprises both open reading frames, where454B is in the 5′ region, and about 2 kb down from it is 454A.

[0023] PCP0557 (SEQ ID 18-19): polypeptides comprising, consisting of,or consisting essentially of about amino acids 1-237, polypeptidefragments thereof, and polynucleotides encoding said polypeptides.PCP0557 polypeptide has a phosphoacceptor domain indicating that it isinvolved in signal transduction. This domain (e.g., amino acids 565-620)can be used as a substrate in kinase assays, e.g., as described in Kempet al., “Design and use of peptide substrates for protein kinases,”Methods in Enzymol., 200:121-34, 1991; Wang et al., “Identification ofthe major site of rat prolactin phosphorylation as serine 177,” J. Biol.Chem., 271:2462-9, 1996; Yasuda et al., “A synthetic peptide substratefor selective assay of protein kinase C,” Biochem. Biophys. Res. Comm.,166:1220-7, 1990; Gonzalez et al., “Use of the synthetic peptideneurogranin(28-43) as a selective protein kinase C substrate in assaysof tissue homogenates,” Anal. Biochem., 215:184-9, 1993; Parker et al.,“Development of high throughput screening assays using fluorescencepolarization: nuclear receptor-ligand-binding and kinase/phosphataseassays,” J. Biomol. Screen., 5:77-88, April 2000. See, also., U.S. Pat.Nos. 6,203,994, 6,074,861, 6,066,462, 6,004,757, and 5,741,689.

[0024] PCP0762 (SEQ ID NO 24-25): polypeptides comprising, consistingof, or consisting essentially of about amino acids 82-86, 113-221,polypeptide fragments thereof, and polynucleotides encoding saidpolypeptides. It contains a SCAN domain involved in transcriptionalregulation.

[0025] PCP0806 (SEQ ID NO 26-27): polypeptides comprising, consistingof, or consisting essentially of about amino acids 31-32, polypeptidefragments thereof, and polynucleotides encoding said polypeptides.PC0806 is in an intracellular protein that shows high expression inlung, pancreas, prostate, and stomach.

[0026] PCP0815A (SEQ ID NO 28-29): polypeptides comprising, consistingof, or consisting essentially of about amino acids 1-24, 131-1005, 744,polypeptide fragments thereof, and polynucleotides encoding saidpolypeptides; PCP0815C (SEQ ID NO 30-31): polypeptides comprising,consisting of, or consisting essentially of about amino acids 1-24,polypeptide fragments thereof, and polynucleotides encoding saidpolypeptides. The gene is expressed in many tissues, but is highest inbrain and pituitary. PCP0815A comprises seven zinc finger domains,indicating that it is a transcriptional regulator. PCP0815C is missingthese transcriptional domains, indicating that it is a regulator (e.g.,a negative regulator) of PCP0815A.

[0027] PCP0664 is a 122 amino acid polypeptide comprising an N-terminalhydrophobic region. It has a signal peptide cleavage site at aboutbetween amino acids 18 and 19, indicating that it can be a secretedmolecule.

[0028] Nucleic Acids

[0029] In accordance with the present invention, genes have beenidentified which are differentially expressed in prostate cancer. Thesegenes can be further divided into groups based on additionalcharacteristics of their expression and the tissues in which they areexpressed. For instance, genes can be further subdivided based on thestage and/or grade of the cancer in which they are expressed. Genes canalso be grouped based on their penetrance in a prostate cancer, e.g.,expressed in all prostate cancer examined, expressed in a certainpercentage of prostate cancer examined, etc. These groupings do notrestrict or limit the use such genes in therapeutic, diagnostic,prognostic, etc., applications. For instance, a gene which is expressedin only some cancers (e.g., incompletely penetrant) may be useful intherapeutic applications to treat a subset of cancers. Similarly, aco-penetrant gene, or a gene which is expressed in prostate cancer andother normal tissues, may be useful as a therapeutic or diagnostic, evenif its expression pattern is not highly prostate specific. Thus, theuses of the genes or their products are not limited by their patterns ofexpression.

[0030] By the phrase “differential expression,” it is meant that thelevels of expression of a gene, as measured by its transcription ortranslation product, are different depending upon the specific cell-typeor tissue (e.g., in an averaging assay that looks at a population ofcells). There are no absolute amounts by which the gene expressionlevels must vary, as long as the differences are measurable.

[0031] The phrase “up-regulated” indicates that an mRNA transcript orother nucleic acid corresponding to a polynucleotide of the presentinvention is expressed in larger amounts in a cancer as compared to thesame transcript expressed in normal cells from which the cancer wasderived. In general, up-regulation can be assessed by any suitablemethod, including any of the nucleic acid detection and hybridizationmethods mentioned below, as well as polypeptide-based methods.Up-regulation also includes going from substantially no expression in anormal tissue, from detectable expression in a normal tissue, fromsignificant expression in a normal tissue, to higher levels in thecancer.

[0032] The phrase “down-regulated” indicates that an mRNA transcript orother nucleic acid corresponding to a polynucleotide of the presentinvention is expressed in lower amounts in a cancer as compared to thesame transcript expressed in normal cells from which the cancer wasderived. A down-regulated gene can show no detectable expression, or anyamount of expression which is less than the gene's expression in normaltissue.

[0033] Differential regulation can be determined by any suitable method,e.g., by comparing its abundance per gram of RNA (e.g., total RNA,polyadenylated mRNA, etc.) extracted from a prostate tissue incomparison to the corresponding normal tissue. The normal tissue can befrom the same or different individual or source. For convenience, it canbe supplied as a separate component or in a kit in combination withprobes and other reagents for detecting genes. The quantity by which anucleic acid is differentially-regulated can be any value, e.g., about10% more or less of normal expression, about 50% more or less of normalexpression, 2-fold more or less, 5-fold more or less, 10-fold more orless, etc.

[0034] The amount of transcript can also be compared to a different genein the same sample, especially a gene whose abundance is known andsubstantially no different in its expression between normal and cancercells (e.g., a “control” gene). If represented as a ratio, with thequantity of differentially-regulated gene transcript in the numeratorand the control gene transcript in the denominator, the ratio would belarger, e.g., in prostate cancer than in a sample from normal prostatetissue.

[0035] Differential-regulation can arise through a number of differentmechanisms. The present invention is not bound by any specific waythrough which it occurs. Differential-regulation of a polynucleotide canoccur, e.g., by modulating (1) transcriptional rate of the gene (e.g.,increasing its rate, inducing or stimulating its transcription from abasal, low-level rate, etc.), (2) the post-transcriptional processing ofRNA transcripts, (3) the transport of RNA from the nucleus into thecytoplasm, (4) the RNA nuclear and cytoplasmic turnover (e.g., by virtueof having higher stability or resistance to degradation), andcombinations thereof. See, e.g., Tollervey and Caceras, Cell,103:703-709, 2000.

[0036] A differentially-regulated polynucleotide is useful in a varietyof different applications as described in greater details below. Becauseit is more abundant in cancer, it and its expression products can beused in a diagnostic test to assay for the presence of cancer, e.g., intissue sections, in a biopsy sample, in total RNA, in lymph, in blood,etc. Differentially-regulated polynucleotides and polypeptides can beused individually, or in groups, to assess the cancer, e.g., todetermine the specific type of cancer, its stage of development, thenature of the genetic defect, etc., or to assess the efficacy of atreatment modality. How to use polynucleotides in diagnostic andprognostic assays is discussed below. In addition, the polynucleotidesand the polypeptides they encode, can serve as a target for therapy ordrug discovery. A polypeptide, coded for by a differentially-regulatedpolynucleotide, which is displayed on the cell-surface, can be a targetfor immunotherapy to destroy, inhibit, etc., the diseased tissue.Differentially-regulated transcripts can also be used in drug discoveryschemes to identify pharmacological agents which suppress, inhibit,etc., their differential-regulation, thereby preventing the phenotypeassociated with their expression. Thus, a differentially-regulatedpolynucleotide and its expression products of the present invention havesignificant applications in diagnostic, therapeutic, prognostic, drugdevelopment, and related areas.

[0037] The expression patterns of the differentially expressed genesdisclosed herein can be described as a “fingerprint” in that they are adistinctive pattern displayed by a cancer. Just as with a fingerprint,an expression pattern can be used as a unique identifier to characterizethe status of a tissue sample. The list of genes represented by SEQ IDNOS 1-31 provides an example of a cell expression profile for a prostatecancer. It can be used as a point of reference to compare andcharacterize unknown samples and samples for which further informationis sought. Tissue fingerprints can be used in many ways, e.g., toclassify an unknown tissue as being a prostate cancer, to determine theorigin of a particular cancer (e.g., the origin of metastatic cells), todetermine the presence of a cancer in a biopsy sample, to assess theefficacy of a cancer therapy in a human patient or a non-human animalmodel, to detect circulating cancer cells in blood or a lymph nodebiopsy, etc. While the expression profile of the complete gene setrepresented by SEQ ID NOS 1-31 may be most informative, a fingerprintcontaining expression information from less than the full collection canbe useful, as well. In the same way that an incomplete fingerprint maycontain enough of the pattern of whorls, arches, loops, and ridges, toidentify the individual, a cell expression fingerprint containing lessthan the full complement may be adequate to provide useful and uniqueidentifying and other information about the sample. Moreover, cancer isa multifactorial disease, involving genetic aberrations in more thangene locus. This multifaceted nature may be reflected in different cellexpression profiles associated with prostate cancers arising indifferent individuals, in different locations in the same individual, oreven within the same cancer locus. As a result, a complete match with aparticular cell expression profile, as shown herein, is not necessary toclassify a cancer as being of the same type or stage. Similarity to onecell expression profile, e.g., as compared to another, can be adequateto classify cancer types, grades, and stages.

[0038] A mammalian polynucleotide, or fragment thereof, of the presentinvention is a polynucleotide having a nucleotide sequence obtainablefrom a natural source. When the species name is used, e.g., human, itindicates that the polynucleotide or polypeptide is obtainable from anatural source. It therefore includes naturally-occurring normal Ittherefore includes naturally-occurring normal, naturally-occurringmutant, and naturally-occurring polymorphic alleles (e.g., SNPs),differentially-spliced transcripts, splice-variants, etc. By the term“naturally-occurring,” it is meant that the polynucleotide is obtainablefrom a natural source, e.g., animal tissue and cells, body fluids,tissue culture cells, forensic samples. Natural sources include, e.g.,living cells obtained from tissues and whole organisms, tumors, culturedcell lines, including primary and immortalized cell lines.Naturally-occurring mutations can include deletions (e.g., a truncatedamino- or carboxy-terminus), substitutions, inversions, or additions ofnucleotide sequence. These genes can be detected and isolated bypolynucleotide hybridization according to methods which one skilled inthe art would know, e.g., as discussed below.

[0039] A polynucleotide according to the present invention can beobtained from a variety of different sources. It can be obtained fromDNA or RNA, such as polyadenylated mRNA or total RNA, e.g., isolatedfrom tissues, cclls, or whole organism. The polynucleotide can beobtained directly from DNA or RNA, from a cDNA library, from a genomiclibrary, etc. The polynucleotide can be obtained from a cell or tissue(e.g., from an embryonic or adult tissues) at a particular stage ofdevelopment, having a desired genotype, phenotype, disease status, etc.A polynucleotide which “codes without interruption” refers to apolynucleotide having a continuous open reading frame (“ORF”) ascompared to an ORF which is interrupted by introns or other noncodingsequences.

[0040] Polynucleotides and polypeptides (including any part of regulatedprostate gene) can be excluded as compositions from the presentinvention if, e.g., listed in a publicly available databases on the daythis application was filed and/or disclosed in a patent applicationhaving an earlier filing or priority date than this application and/orconceived and/or reduced to practice earlier than a polynucleotide inthis application.

[0041] As described herein, the phrase “an isolated polynucleotide whichis SEQ ID NO,” or “an isolated polynucleotide which is selected from SEQID NO,” refers to an isolated nucleic acid molecule from which therecited sequence was derived (e.g., a cDNA derived from mRNA; cDNAderived from genomic DNA). Because of sequencing errors, typographicalerrors, etc., the actual naturally-occurring sequence may differ from aSEQ ID listed herein. Thus, the phrase indicates the specific moleculefrom which the sequence was derived, rather than a molecule having thatexact recited nucleotide sequence, analogously to how a culturedepository number refers to a specific cloned fragment in a cryotube.

[0042] As explained in more detail below, a polynucleotide sequence ofthe invention can contain the complete sequence as shown in SEQ ID NOS1, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30,degenerate sequences thereof, anti-sense, muteins thereof, genescomprising said sequences, full-length cDNAs comprising said sequences,complete genomic sequences, fragments thereof, homologs, primers,nucleic acid molecules which hybridize thereto, derivatives thereof,etc.

[0043] Genomic

[0044] The present invention also relates genomic DNA from which thepolynucleotides of the present invention can be derived. A genomic DNAcoding for a human, mouse, or other mammalian polynucleotide, can beobtained routinely, for example, by screening a genomic library (e.g., aYAC library) with a polynucleotide of the present invention, or bysearching nucleotide databases, such as GenBank and EMBL, for matches.Promoter and other regulatory regions (including both 5′ and 3′ regions,as well introns) can be identified upstream or downstream of coding andexpressed RNAs, and assayed routinely for activity, e.g., by joining toa reporter gene (e.g., CAT, GFP, alkaline phosphatase, luciferase,galatosidase). A promoter obtained from a prostate selective gene can beused, e.g., in gene therapy to obtain tissue-specific expression of aheterologous gene (e.g., coding for a therapeutic product or cytotoxin).5′ and 3′ sequences (including, UTRs and introns) can be used tomodulate or regulate stability, transcription, and translation ofnucleic acids, including the sequence to which is attached in nature, aswell as heterologous nucleic acids.

[0045] Constructs

[0046] A polynucleotide of the present invention can comprise additionalpolynucleotide sequences, e.g., sequences to enhance expression,detection, uptake, cataloging, tagging, etc. A polynucleotide caninclude only coding sequence; a coding sequence and additionalnon-naturally occurring or heterologous coding sequence (e.g., sequencescoding for leader, signal, secretory, targeting, enzymatic, fluorescent,antibiotic resistance, and other functional or diagnostic peptides);coding sequences and non-coding sequences, e.g., untranslated sequencesat either a 5′ or 3′ end, or dispersed in the coding sequence, e.g.,introns.

[0047] A polynucleotide according to the present invention also cancomprise an expression control sequence operably linked to apolynucleotide as described above. The phrase “expression controlsequence” means a polynucleotide sequence that regulates expression of apolypeptide coded for by a polynucleotide to which it is functionally(“operably”) linked. Expression can be regulated at the level of themRNA or polypeptide. Thus, the expression control sequence includesmRNA-related elements and protein-related elements. Such elementsinclude promoters, enhancers (viral or cellular), ribosome bindingsequences, transcriptional terminators, etc. An expression controlsequence is operably linked to a nucleotide coding sequence when theexpression control sequence is positioned in such a manner to effect orachieve expression of the coding sequence. For example, when a promoteris operably linked 5′ to a coding sequence, expression of the codingsequence is driven by the promoter. Expression control sequences caninclude an initiation codon and additional nucleotides to place apartial nucleotide sequence of the present invention in-frame in orderto produce a polypeptide (e.g., pET vectors from Promega have beendesigned to permit a molecule to be inserted into all three readingframes to identify the one that results in polypeptide expression).Expression control sequences can be heterologous or endogenous to thenormal gene.

[0048] A polynucleotide of the present invention can also comprisenucleic acid vector sequences, e.g., for cloning, expression,amplification, selection, etc. Any effective vector can be used. Avector is, e.g., a polynucleotide molecule which can replicateautonomously in a host cell, e.g., containing an origin of replication.Vectors can be useful to perform manipulations, to propagate, and/orobtain large quantities of the recombinant molecule in a desired host. Askilled worker can select a vector depending on the purpose desired,e.g., to propagate the recombinant molecule in bacteria, yeast, insect,or mammalian cells. The following vectors are provided by way ofexample. Bacterial: pQE70, pQE60, pQE-9 (Qiagen), pBS, pD10,Phagescript, phiX174, pBK Phagemid, pNH8A, pNH16a, pNH18Z, pNH46A(Stratagene); Bluescript KS+II (Stratagene); ptrc99a, pKK223-3,pKK233-3, pDR54 0, pRIT5 (Pharmacia). Eukaryotic: PWLNEO, pSV2CAT,pOG44, pXT1, pSG (Stratagene), pSVK3, PBPV, PMSG, pSVL (Pharmacia),pCR2.1/TOPO, pCRII/TOPO, pCR4/TOPO, pTrcHisB, pCMV6-XL4, etc. However,any other vector, e.g., plasmids, viruses, or parts thereof, may be usedas long as they are replicable and viable in the desired host. Thevector can also comprise sequences which enable it to replicate in thehost whose genome is to be modified.

[0049] Hybridization

[0050] Polynucleotide hybridization, as discussed in more detail below,is useful in a variety of applications, including, in gene detectionmethods, for identifying mutations, for making mutations, to identifyhomologs in the same and different species, to identify related membersof the same gene family, in diagnostic and prognostic assays, intherapeutic applications (e.g., where an antisense polynucleotide isused to inhibit expression), etc.

[0051] The ability of two single-stranded polynucleotide preparations tohybridize together is a measure of their nucleotide sequencecomplementarity, e.g., base-pairing between nucleotides, such as A-T,G-C, etc. The invention thus also relates to polynucleotides, and theircomplements, which hybridize to a polynucleotide comprising a nucleotidesequence as set forth in SEQ ID NOS 1, 3, 4, 6, 8, 10, 12, 14, 16, 18,20, 22, 24, 26, 28, and 30 and genomic sequences thereof. A nucleotidesequence hybridizing to the latter sequence will have a complementarypolynucleotide strand, or act as a template for one in the presence of apolymerase (i.e., an appropriate polynucleotide synthesizing enzyme).The present invention includes both strands of polynucleotide, e.g., asense strand and an anti-sense strand.

[0052] Hybridization conditions can be chosen to select polynucleotideswhich have a desired amount of nucleotide complementarity with thenucleotide sequences set forth in SEQ ID NOS 1, 3, 4, 6, 8, 10, 12, 14,16, 18, 20, 22, 24, 26, 28, and 30 and genomic sequences thereof. Apolynucleotide capable of hybridizing to such sequence, preferably,possesses, e.g., about 70%, 75%, 80%, 85%, 87%, 90%, 92%, 95%, 97%, 99%,or 100% complementarity, between the sequences. The present inventionparticularly relates to polynucleotide sequences which hybridize to thenucleotide sequences set forth in SEQ ID NOS 1, 3, 4, 6, 8, 10, 12, 14,16, 18, 20, 22, 24, 26, 28, and 30 or genomic sequences thereof, underlow or high stringency conditions. These conditions can be used, e.g.,to select corresponding homologs in non-human species.

[0053] Polynucleotides which hybridize to polynucleotides of the presentinvention can be selected in various ways. Filter-type blots (i.e.,matrices containing polynucleotide, such as nitrocellulose), glasschips, and other matrices and substrates comprising polynticleotides(short or long) of interest, can be incubated in a prehybridizationsolution (e.g., 6×SSC, 0.5% SDS, 100 μg/ml denatured salmon sperm DNA,5×Denhardt's solution, and 50% formamide), at 22-68° C., overnight, andthen hybridized with a detectable polynucleotide probe under conditionsappropriate to achieve the desired stringency. In general, when highhomology or sequence identity is desired, a high temperature can be used(e.g., 65° C.). As the homology drops, lower washing temperatures areused. For salt concentrations, the lower the salt concentration, thehigher the stringency. The length of the probe is another consideration.Very short probes (e.g., less than 100 base pairs) are washed at lowertemperatures, even if the homology is high. With short probes, formamidecan be omitted. See, e.g., Current Protocols in Molecular Biology,Chapter 6, Screening of Recombinant Libraries; Sambrook et al.,Molecular Cloning, 1989, Chapter 9.

[0054] For instance, high stringency conditions can be achieved byincubating the blot overnight (e.g., at least 12 hours) with a longpolynucleotide probe in a hybridization solution containing, e.g., about5×SSC, 0.5% SDS, 100 μg/ml denatured salmon sperm DNA and 50% formamide,at 42° C. Blots can be washed at high stringency conditions that allow,e.g., for less than 5% bp mismatch (e.g., wash twice in 0.1% SSC and0.1% SDS for 30 min at 65° C.), i.e., selecting sequences having 95% orgreater sequence identity.

[0055] Other non-limiting examples of high stringency conditionsincludes a final wash at 65° C. in aqueous buffer containing 30 mM NaCland 0.5% SDS. Another example of high stringent conditions ishybridization in 7% SDS, 0.5 M NaPO₄, pH 7, 1 mM EDTA at 50° C., e.g.,overnight, followed by one or more washes with a 1% SDS solution at 42°C. Whereas high stringency washes can allow for less than 5% mismatch,reduced or low stringency conditions can permit up to 20% nucleotidemismatch. Hybridization at low stringency can be accomplished as above,but using lower formamide conditions, lower temperatures and/or lowersalt concentrations, as well as longer periods of incubation time.

[0056] Hybridization can also be based on a calculation of meltingtemperature (Tm) of the hybrid formed between the probe and its target,as described in Sambrook et al. Generally, the temperature Tm at which ashort oligonucleotide (containing 18 nucleotides or fewer) will meltfrom its target sequence is given by the following equation: Tm=(numberof A's and T's)×2° C.+(number of C's and G's)×4° C. For longermolecules, Tm=81.5+16.6 log₁₀[Na⁺]+0.41(% GC)−600/N where [Na⁺] is themolar concentration of sodium ions, % GC is the percentage of GC basepairs in the probe, and N is the length. Hybridization can be carriedout at several degrees below this temperature to ensure that the probeand target can hybridize. Mismatches can be allowed for by lowering thetemperature even further.

[0057] Stringent conditions can be selected to isolate sequences, andtheir complements, which have, e.g., at least about 90%, 95%, or 97%,nucleotide complementarity between the probe (e.g., a shortpolynucleotide of SEQ ID NOS 1, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22,24, 26, 28, and 30 or genomic sequences thereof) and a targetpolynucleotide.

[0058] Other homologs of polynucleotides of the present invention can beobtained from mammalian and non-mammalian sources according to variousmethods. For example, hybridization with a polynucleotide can beemployed to select homologs, e.g., as described in Sambrook et al.,Molecular Cloning, Chapter 11, 1989. Such homologs can have varyingamounts of nucleotide and amino acid sequence identity and similarity tosuch polynucleotides of the present invention. Mammalian organismsinclude, e.g., mice, rats, monkeys, pigs, cows, etc. Non-mammalianorganisms include, e.g., vertebrates, invertebrates, zebra fish,chicken, Drosophila, C. elegans, Xenopus, yeast such as S. pombe, S.cerevisiae, roundworms, prokaryotes, plants, Arabidopsis, artemia,viruses, etc. The degree of nucleotide sequence identity between humanand mouse can be about, e.g. 70% or more, 85% or more for open readingframes, etc.

[0059] Alignment

[0060] Alignments can be accomplished by using any effective algorithm.For pairwise alignments of DNA sequences, the methods described byWilbur-Lipman (e.g., Wilbur and Lipman, Proc. Natl. Acad. Sci.,80:726-730, 1983) or Martinez/Needleman-Wunsch (e.g., Martinez, NucleicAcid Res., 11:4629-4634, 1983) can be used. For instance, if theMartinez/Needleman-Wunsch DNA alignment is applied, the minimum matchcan be set at 9, gap penalty at 1.10, and gap length penalty at 0.33.The results can be calculated as a similarity index, equal to the sum ofthe matching residues divided by the sum of all residues and gapcharacters, and then multiplied by 100 to express as a percent.Similarity index for related genes at the nucleotide level in accordancewith the present invention can be greater than 70%, 80%, 85%, 90%, 95%,99%, or more. Pairs of protein sequences can be aligned by theLipman-Pearson method (e.g., Lipman and Pearson, Science, 227:1435-1441,1985) with k-tuple set at 2, gap penalty set at 4, and gap lengthpenalty set at 12. Results can be expressed as percent similarity index,where related genes at the amino acid level in accordance with thepresent invention can be greater than 65%, 70%, 75%, 80%, 85%, 90%, 95%,99%, or more. Various commercial and free sources of alignment programsare available, e.g., MegAlign by DNA Star, BLAST (National Center forBiotechnology Information), BCM (Baylor College of Medicine) Launcher,etc. BLAST can be used to calculate amino acid sequence identity, aminoacid sequence homology, and nucleotide sequence identity. Thesecalculations can be made along the entire length of each of the targetsequences which are to be compared.

[0061] After two sequences have been aligned, a “percent sequenceidentity” can be determined. For these purposes, it is convenient torefer to a Reference Sequence and a Compared Sequence, where theCompared Sequence is compared to the Reference Sequence. Percentsequence identity can be determined according to the following formula:Percent Identity=100[1−(C/R)], wherein C is the number of differencesbetween the Reference Sequence and the Compared Sequence over the lengthof alignment between the Reference Sequence and the Compared Sequencewhere (i) each base or amino acid in the Reference Sequence that doesnot have a corresponding aligned base or amino acid in the ComparedSequence, (ii) each gap in the Reference Sequence, (iii) each alignedbase or amino acid in the Reference Sequence that is different from analigned base or amino acid in the Compared Sequence, constitutes adifference; and R is the number of bases or amino acids in the ReferenceSequence over the length of the alignment with the Compared Sequencewith any gap created in the Reference Sequence also being counted as abase or amino acid.

[0062] Percent sequence identity can also be determined by otherconventional methods, e.g., as described in Altschul et al., Bull. Math.Bio. 48: 603-616, 1986 and Henikoff and Henikoff, Proc. Natl. Acad. Sci.USA 89:10915-10919, 1992.

[0063] Specific Polynucleotide Probes

[0064] A polynucleotide of the present invention can comprise anycontinuous nucleotide sequence of SEQ ID NOS 1, 3, 4, 6, 8, 10, 12, 14,16, 18, 20, 22, 24, 26, 28, and 30, sequences which share sequenceidentity thereto, or complements thereof. The term “probe” refers to anysubstance that can be used to detect, identify, isolate, etc., anothersubstance. A polynucleotide probe is comprised of nucleic acid can beused to detect, identify, etc., other nucleic acids, such as DNA andRNA.

[0065] These polynucleotides can be of any desired size that iseffective to achieve the specificity desired. For example, a probe canbe from about 7 or 8 nucleotides to several thousand nucleotides,depending upon its use and purpose. For instance, a probe used as aprimer PCR can be shorter than a probe used in an ordered array ofpolynucleotide probes. Probe sizes vary, and the invention is notlimited in any way by their size, e.g., probes can be from about 7-2000nucleotides, 7-1000, 8-700, 8-600, 8-500, 8-400, 8-300, 8-150, 8-100,8-75, 7-50, 10-25, 14-16, at least about 8, at least about 10, at leastabout 15, at least about 25, etc. The polynucleotides can havenon-naturally-occurring nucleotides, e.g., inosine, AZT, 3TC, etc. Thepolynucleotides can have 100% sequence identity or complementarity to asequence of SEQ ID NOS 1, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24,26, 28, and 30, or it can have mismatches or nucleotide substitutions,e.g., 1, 2, 3, 4, or 5 substitutions. The probes can be single-strandedor double-stranded.

[0066] In accordance with the present invention, a polynucleotide can bepresent in a kit, where the kit includes, e.g., one or morepolynucleotides, a desired buffer (e.g., phosphate, tris, etc.),detection compositions, RNA or cDNA from different tissues to be used ascontrols, libraries, etc. The polynucleotide can be labeled orunlabeled, with radioactive or non-radioactive labels as known in theart. Kits can comprise one or more pairs of polynucleotides foramplifying nucleic acids specific for differentially-regulated genes ofthe present invention, e.g., comprising a forward and reverse primereffective in PCR. These include both sense and anti-sense orientations.For instance, in PCR-based methods (such as RT-PCR), a pair of primersare typically used, one having a sense sequence and the other having anantisense sequence.

[0067] Another aspect of the present invention is a nucleotide sequencethat is specific to, or for, a selective polynucleotide. The phrases“specific for” or “specific to” a polynucleotide have a functionalmeaning that the polynucleotide can be used to identify the presence ofone or more target genes in a sample and distinguish them fromnon-target genes. It is specific in the sense that it can be used todetect polynucleotides above background noise (“non-specific binding”).A specific sequence is a defined order of nucleotides (or amino acidsequences, if it is a polypeptide sequence) which occurs in thepolynucleotide, e.g., in the nucleotide sequences of SEQ ID NOS 1, 3, 4,6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30, and which ischaracteristic of that target sequence, and substantially no non-targetsequences. A probe or mixture of probes can comprise a sequence orsequences that are specific to a plurality of target sequences, e.g.,where the sequence is a consensus sequence, a functional domain, etc.,e.g., capable of recognizing a family of related genes. Such sequencescan be used as probes in any of the methods described herein orincorporated by reference. Both sense and antisense nucleotide sequencesare included. A specific polynucleotide according to the presentinvention can be determined routinely.

[0068] A polynucleotide comprising a specific sequence can be used as ahybridization probe to identify the presence of, e.g., human or mousepolynucleotide, in a sample comprising a mixture of polynucleotides,e.g., on a Northern blot. Hybridization can be performed under highstringent conditions (see, above) to select polynucleotides (and theircomplements which can contain the coding sequence) having at least 90%,95%, 99%, etc., identity (i.e., complementarity) to the probe, but lessstringent conditions can also be used. A specific polynucleotidesequence can also be fused in-frame, at either its 5′ or 3′ end, tovarious nucleotide sequences as mentioned throughout the patent,including coding sequences for enzymes, detectable markers, GFP, etc,expression control sequences, etc.

[0069] A polynucleotide probe, especially one that is specific to apolynucleotide of the present invention, can be used in gene detectionand hybridization methods as already described. In one embodiment, aspecific polynucleotide probe can be used to detect whether a particulartissue or cell-type is present in a target sample. To carry out such amethod, a selective polynucleotide can be chosen which is characteristicof the desired target tissue. Such polynucleotide is preferably chosenso that it is expressed or displayed in the target tissue, but not inother tissues which are present in the sample. For instance, ifdetection of prostate is desired, it may not matter whether theselective polynucleotide is expressed in other tissues, as long as it isnot expressed in cells normally present in blood, e.g., peripheral bloodmononuclear cells. Starting from the selective polynucleotide, aspecific polynucleotide probe can be designed which hybridizes (ifhybridization is the basis of the assay) under the hybridizationconditions to the selective polynucleotide, whereby the presence of theselective polynucleotide can be determined.

[0070] Probes which are specific for polynucleotides of the presentinvention can also be prepared using involve transcription-basedsystems, e.g., incorporating an RNA polymerase promoter into a selectivepolynucleotide of the present invention, and then transcribinganti-sense RNA using the polynucleotide as a template. See, e.g., U.S.Pat. No. 5,545,522.

[0071] Polynucleotide Composition

[0072] A polynucleotide according to the present invention can comprise,e.g., DNA, RNA, synthetic polynucleotide, peptide polynucleotide,modified nucleotides, dsDNA, ssDNA, ssRNA, dsRNA, and mixtures thereof.A polynucleotide can be single- or double-stranded, triplex, DNA:RNA,duplexes, comprise hairpins, and other secondary structures, etc.Nucleotides comprising a polynucleotide can be joined via various knownlinkages, e.g., ester, sulfamate, sulfamide, phosphorothioate,phosphoramidate, methylphosphonate, carbamate, etc., depending on thedesired purpose, e.g., resistance to nucleases, such as RNAse H,improved in vivo stability, etc. See, e.g., U.S. Pat. No. 5,378,825. Anydesired nucleotide or nucleotide analog can be incorporated, e.g.,6-mercaptoguanine, 8-oxo-guanine, etc.

[0073] Various modifications can be made to the polynucleotides, such asattaching detectable markers (avidin, biotin, radioactive elements,fluorescent tags and dyes, energy transfer labels, energy-emittinglabels, binding partners, etc.) or moieties which improve hybridization,detection, and/or stability. The polynucleotides can also be attached tosolid supports, e.g., nitrocellulose, magnetic or paramagneticmicrospheres (e.g., as described in U.S. Pat. No. 5,411,863; U.S. Pat.No. 5,543,289; for instance, comprising ferromagnetic, supermagnetic,paramagnetic, superparamagnetic, iron oxide and polysaccharide), nylon,agarose, diazotized cellulose, latex solid microspheres,polyacrylamides, etc., according to a desired method. See, e.g., U.S.Pat. Nos. 5,470,967, 5,476,925, and 5,478,893.

[0074] Polynucleotide according to the present invention can be labeledaccording to any desired method. The polynucleotide can be labeled usingradioactive tracers such as ³²P, ³⁵S, ³H, or ¹⁴C, to mention somecommonly used tracers. The radioactive labeling can be carried outaccording to any method, such as, for example, terminal labeling at the3′ or 5′ end using a radiolabeled nucleotide, polynucleotide kinase(with or without dephosphorylation with a phosphatase) or a ligase(depending on the end to be labeled). A non-radioactive labeling canalso be used, combining a polynucleotide of the present invention withresidues having immunological properties (antigens, haptens), a specificaffinity for certain reagents (ligands), properties enabling detectableenzyme reactions to be completed (enzymes or coenzymes, enzymesubstrates, or other substances involved in an enzymatic reaction), orcharacteristic physical properties, such as fluorescence or the emissionor absorption of light at a desired wavelength, etc.

[0075] Nucleic Acid Detection Methods

[0076] Another aspect of the present invention relates to methods andprocesses for detecting differentially-regulated genes of the presentinvention. Detection methods have a variety of applications, includingfor diagnostic, prognostic, forensic, and research applications. Toaccomplish gene detection, a polynucleotide in accordance with thepresent invention can be used as a “probe.” The term “probe” or“polynucleotide probe” has its customary meaning in the art, e.g., apolynucleotide which is effective to identify (e.g., by hybridization),when used in an appropriate process, the presence of a targetpolynucleotide to which it is designed. Identification can involvesimply determining presence or absence, or it can be quantitative, e.g.,in assessing amounts of a gene or gene transcript present in a sample.Probes can be useful in a variety of ways, such as for diagnosticpurposes, to identify homologs, and to detect, quantitate, or isolate apolynucleotide of the present invention in a test sample.

[0077] Assays can be utilized which permit quantification and/orpresence/absence detection of a target nucleic acid in a sample. Assayscan be performed at the single-cell level, or in a sample comprisingmany cells, where the assay is “averaging” expression over the entirecollection of cells and tissue present in the sample. Any suitable assayformat can be used, including, but not limited to, e.g., Southern blotanalysis, Northern blot analysis, polymerase chain reaction (“PCR”)(e.g., Saiki et al., Science, 241:53, 1988; U.S. Pat. Nos. 4,683,195,4,683,202, and 6,040,166; PCR Protocols: A Guide to Methods andApplications, Innis et al., eds., Academic Press, New York, 1990),reverse transcriptase polymerase chain reaction (“RT-PCR”), anchoredPCR, rapid amplification of cDNA ends (“RACE”) (e.g., Schaefer in GeneCloning and Analysis: Current Innovations, Pages 99-115, 1997), ligasechain reaction (“LCR”) (EP 320 308), one-sided PCR (Ohara et al., Proc.Natl. Acad. Sci., 86:5673-5677, 1989), indexing methods (e.g., U.S. Pat.No. 5,508,169), in situ hybridization, differential display (e.g., Lianget al., Nucl. Acid. Res., 21:3269-3275, 1993; U.S. Pat. Nos. 5,262,311,5,599,672 and 5,965,409; WO97/18454; Prashar and Weissman, Proc. Natl.Acad. Sci., 93:659-663, and U.S. Pat. Nos. 6,010,850 and 5,712,126;Welsh et al., Nucleic Acid Res., 20:4965-4970, 1992, and U.S. Pat. No.5,487,985) and other RNA fingerprinting techniques, nucleic acidsequence based amplification (“NASBA”) and other transcription basedamplification systems (e.g., U.S. Pat. Nos. 5,409,818 and 5,554,527; WO88/10315), polynucleotide arrays (e.g., U.S. Pat. Nos. 5,143,854,5,424,186; 5,700,637, 5,874,219, and 6,054,270; PCT WO 92/10092; PCT WO90/15070), Qbeta Replicase (PCT/US87/00880), Strand DisplacementAmplification (“SDA”), Repair Chain Reaction (“RCR”), nucleaseprotection assays, subtraction-based methods, Rapid-Scan™, etc.Additional useful methods include, but are not limited to, e.g.,template-based amplification methods, competitive PCR (e.g., U.S. Pat.No. 5,747,251), redox-based assays (e.g., U.S. Pat. No. 5,871,918),Taqman-based assays (e.g., Holland et al., Proc. Natl. Acad, Sci.,88:7276-7280, 1991; U.S. Pat. Nos. 5,210,015 and 5,994,063), real-timefluorescence-based monitoring (e.g., U.S. Pat. No. 5,928,907), molecularenergy transfer labels (e.g., U.S. Pat. Nos. 5,348,853, 5,532,129,5,565,322, 6,030,787, and 6,117,635; Tyagi and Kramer, Nature Biotech.,14:303-309, 1996). Any method suitable for single cell analysis of geneor protein expression can be used, including in situ hybridization,immunocytochemistry, MACS, FACS, flow cytometry, etc. For single cellassays, expression products can be measured using antibodies, PCR, orother types of nucleic acid amplification (e.g., Brady et al., MethodsMol. & Cell. Biol. 2, 17-25, 1990; Eberwine et al., 1992, Proc. Natl.Acad. Sci., 89, 3010-3014, 1992; U.S. Pat. No. 5,723,290). These andother methods can be carried out conventionally, e.g., as described inthe mentioned publications.

[0078] Many of such methods may require that the polynucleotide islabeled, or comprises a particular nucleotide type useful for detection.The present invention includes such modified polynucleotides that arenecessary to carry out such methods. Thus, polynucleotides can be DNA,RNA, DNA:RNA hybrids, PNA, etc., and can comprise any modification orsubstituent which is effective to achieve detection.

[0079] Detection can be desirable for a variety of different purposes,including research, diagnostic, prognostic, and forensic. For diagnosticpurposes, it may be desirable to identify the presence or quantity of apolynucleotide sequence in a sample, where the sample is obtained fromtissue, cells, body fluids, etc. In a preferred method as described inmore detail below, the present invention relates to a method ofdetecting a polynucleotide comprising, contacting a targetpolynucleotide in a test sample with a polynucleotide probe underconditions effective to achieve hybridization between the target andprobe; and detecting hybridization.

[0080] Any test sample in which it is desired to identify apolynucleotide or polypeptide thereof can be used, including, e.g.,blood, urine, saliva, stool (for extracting nucleic acid, see, e.g.,U.S. Pat. No. 6,177,251), swabs comprising tissue, biopsied tissue,tissue sections, cultured cells, etc.

[0081] Detection can be accomplished in combination with polynucleotideprobes for other genes, e.g., genes which are expressed in other diseasestates, tissues, cells, such as brain, heart, kidney, spleen, thymus,liver, stomach, small intestine, colon, muscle, lung, testis, placenta,pituitary, thyroid, skin, adrenal gland, pancreas, salivary gland,uterus, ovary, prostate gland, peripheral blood cells (T-cells,lymphocytes, etc.), embryo, normal breast, fat, adult and embryonic stemcells, specific cell-types, such as endothelial, epithelial, myocytes,adipose, luminal epithelial, basoepithelial, myoepithelial, stromalcells, etc.

[0082] Polynucleotides can be used in wide range of methods andcompositions, including for detecting, diagnosing, staging, grading,assessing, prognosticating, etc. diseases and disorders associated withdifferentially-regulated genes of the present invention, for monitoringor assessing therapeutic and/or preventative measures, in orderedarrays, etc. Any method of detecting genes and polynucleotides of SEQ IDNOS 1, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30 can beused; certainly, the present invention is not to be limited how suchmethods are implemented.

[0083] Along these lines, the present invention relates to methods ofdetecting differentially-regulated genes described herein in a samplecomprising nucleic acid. Such methods can comprise one or more thefollowing steps in any effective order, e.g., contacting said samplewith a polynucleotide probe under conditions effective for said probe tohybridize specifically to nucleic acid in said sample, and detecting thepresence or absence of probe hybridized to nucleic acid in said sample,wherein said probe is a polynucleotide which is SEQ ID NOS 1, 3, 4, 6,8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30, a polynucleotidehaving, e.g., about 70%, 80%, 85%, 90%, 95%, 99%, or more sequenceidentity thereto, effective or specific fragments thereof, orcomplements thereto. The detection method can be applied to any sample,e.g., cultured primary, secondary, or established cell lines, tissuebiopsy, blood, urine, stool, cerebral spinal fluid, and other bodilyfluids, for any purpose.

[0084] Contacting the sample with probe can be carried out by anyeffective means in any effective environment. It can be accomplished ina solid, liquid, frozen, gaseous, amorphous, solidified, coagulated,colloid, etc., mixtures thereof, matrix. For instance, a probe in anaqueous medium can be contacted with a sample which is also in anaqueous medium, or which is affixed to a solid matrix, or vice-versa.

[0085] Generally, as used throughout the specification, the term“effective conditions” means, e.g., the particular milieu in which thedesired effect is achieved. Such a milieu, includes, e.g., appropriatebuffers, oxidizing agents, reducing agents, pH, co-factors, temperature,ion concentrations, suitable age and/or stage of cell (such as, inparticular part of the cell cycle, or at a particular stage whereparticular genes are being expressed) where cells are being used,culture conditions (including substrate, oxygen, carbon dioxide, etc.).When hybridization is the chosen means of achieving detection, the probeand sample can be combined such that the resulting conditions arefunctional for said probe to hybridize specifically to nucleic acid insaid sample.

[0086] The phrase “hybridize specifically” indicates that thehybridization between single-stranded polynucleotides is based onnucleotide sequence complementarity. The effective conditions areselected such that the probe hybridizes to a preselected and/or definitetarget nucleic acid in the sample. For instance, if detection of apolynucleotide set forth in SEQ ID NOS 1, 3, 4, 6, 8, 10, 12, 14, 16,18, 20, 22, 24, 26, 28, and 30 is desired, a probe can be selected whichcan hybridize to such target gene under high stringent conditions,without significant hybridization to other genes in the sample. Todetect homologs of a polynucleotide set forth in SEQ ID NOS 1, 3, 4, 6,8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30, the effectivehybridization conditions can be less stringent, and/or the probe cancomprise codon degeneracy, such that a homolog is detected in thesample.

[0087] As already mentioned, the methods can be carried out by anyeffective process, e.g., by Northern blot analysis, polymerase chainreaction (PCR), reverse transcriptase PCR, RACE PCR, in situhybridization, etc., as indicated above. When PCR based techniques areused, two or more probes are generally used. One probe can be specificfor a defined sequence which is characteristic of a selectivepolynucleotide, but the other probe can be specific for the selectivepolynucleotide, or specific for a more general sequence, e.g., asequence such as polyA which is characteristic of mRNA, a sequence whichis specific for a promoter, ribosome binding site, or othertranscriptional features, a consensus sequence (e.g., representing afunctional domain). For the former aspects, 5′ and 3′ probes (e.g.,polyA, Kozak, etc.) are preferred which are capable of specificallyhybridizing to the ends of transcripts. When PCR is utilized, the probescan also be referred to as “primers” in that they can prime a DNApolymerase reaction.

[0088] In addition to testing for the presence or absence ofpolynucleotides, the present invention also relates to determining theamounts at which polynucleotides of the present invention are expressedin sample and determining the differential expression of suchpolynucleotides in samples. Such methods can involve substantially thesame steps as described above for presence/absence detection, e.g.,contacting with probe, hybridizing, and detecting hybridized probe, butusing more quantitative methods and/or comparisons to standards.

[0089] The amount of hybridization between the probe and target can bedetermined by any suitable methods, e.g., PCR, RT-PCR, RACE PCR,Northern blot, polynucleotide microarrays, Rapid-Scan, etc., andincludes both quantitative and qualitative measurements. For furtherdetails, see the hybridization methods described above and below.Determining by such hybridization whether the target is differentiallyexpressed (e.g., up-regulated or down-regulated) in the sample can alsobe accomplished by any effective means. For instance, the target'sexpression pattern in the sample can be compared to its pattern in aknown standard, such as in a normal tissue, or it can be compared toanother gene in the same sample. When a second sample is utilized forthe comparison, it can be a sample of normal tissue that is known not tocontain diseased cells. The comparison can be performed on samples whichcontain the same amount of RNA (such as polyadenylated RNA or totalRNA), or, on RNA extracted from the same amounts of starting tissue.Such a second sample can also be referred to as a control or standard.Hybridization can also be compared to a second target in the same tissuesample. Experiments can be performed that determine a ratio between thetarget nucleic acid and a second nucleic acid (a standard or control),e.g., in a normal tissue. When the ratio between the target and controlare substantially the same in a normal and sample, the sample isdetermined or diagnosed not to contain cells. However, if the ratio isdifferent between the normal and sample tissues, the sample isdetermined to contain cancer cells. The approaches can be combined, andone or more second samples, or second targets can be used. Any secondtarget nucleic acid can be used as a comparison, including“housekeeping” genes, such as beta-actin, alcohol dehydrogenase, or anyother gene whose expression does not vary depending upon the diseasestatus of the cell.

[0090] Methods of Identifying Polymorphisms, Mutations, etc., of aDifferentially-Regulated Gene

[0091] Polynucleotides of the present invention can also be utilized toidentify mutant alleles, SNPs, gene rearrangements and modifications,and other polymorphisms of the wild-type gene. Mutant alleles,polymorphisms, SNPs, etc., can be identified and isolated from cancersthat are known, or suspected to have, a genetic component.Identification of such genes can be carried out routinely (see, abovefor more guidance), e.g., using PCR, hybridization techniques, directsequencing, mismatch reactions (see, e.g., above), RFLP analysis, SSCP(e.g., Orita et al., Proc. Natl. Acad. Sci., 86:2766, 1992), etc., wherea polynucleotide having a sequence selected from SEQ ID NOS 1, 3, 4, 6,8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30 is used as a probe.The selected mutant alleles, SNPs, polymorphisms, etc., can be useddiagnostically to determine whether a subject has, or is susceptible toa disorder associated with a differentially-regulated gene, as well asto design therapies and predict the outcome of the disorder. Methodsinvolve, e.g., diagnosing a disorder associated with adifferentially-regulated gene or determining susceptibility to adisorder, comprising, detecting the presence of a mutation in a generepresented by a polynucleotide selected from SEQ ID NOS 1, 3, 4, 6, 8,10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30. The detecting can becarried out by any effective method, e.g., obtaining cells from asubject, determining the gene sequence or structure of a target gene(using, e.g., mRNA, cDNA, genomic DNA, etc), comparing the sequence orstructure of the target gene to the structure of the normal gene,whereby a difference in sequence or structure indicates a mutation inthe gene in the subject. Polynucleotides can also be used to test formutations, SNPs, polymorphisms, etc., e.g., using mismatch DNA repairtechnology as described in U.S. Pat. No. 5,683,877; U.S. Pat. No.5,656,430; Wu et al., Proc. Natl. Acad. Sci., 89:8779-8783, 1992.

[0092] The present invention also relates to methods of detectingpolymorphisms in a differentially-regulated gene, comprising, e.g.,comparing the structure of: genomic DNA comprising all or part of saidgene, mRNA comprising all or part of said gene, cDNA comprising all orpart of said gene, or a polypeptide comprising all or part of said gene,with the structure of said gene as set forth herein. The methods can becarried out on a sample from any source, e.g., cells, tissues, bodyfluids, blood, urine, stool, hair, egg, sperm, etc.

[0093] These methods can be implemented in many different ways. Forexample, “comparing the structure” steps include, but are not limitedto, comparing restriction maps, nucleotide sequences, amino acidsequences, RFLPs, DNAse sites, DNA methylation fingerprints (e.g., U.S.Pat. No. 6,214,556), protein cleavage sites, molecular weights,electrophoretic mobilities, charges, ion mobility, etc., between astandard gene and a test gene. The term “structure” can refer to anyphysical characteristics or configurations which can be used todistinguish between nucleic acids and polypeptides. The methods andinstruments used to accomplish the comparing step depends upon thephysical characteristics which are to be compared. Thus, varioustechniques are contemplated, including, e.g., sequencing machines (bothamino acid and polynucleotide), electrophoresis, mass spectrometer (U.S.Pat. Nos. 6,093,541, 6,002,127), liquid chromatography, HPLC, etc.

[0094] To carry out such methods, “all or part” of the gene orpolypeptide can be compared. For example, if nucleotide sequencing isutilized, the entire gene can be sequenced, including promoter, introns,and exons, or only parts of it can be sequenced and compared, e.g., exon1, exon 2, etc.

[0095] Mutagenesis

[0096] Mutated polynucleotide sequences of the present invention areuseful for various purposes, e.g., to create mutations of thepolypeptides they encode, to identify functional regions of genomic DNA,to produce probes for screening libraries, etc. Mutagenesis can becarried out routinely according to any effective method, e.g.,oligonucleotide-directed (Smith, M., Ann. Rev. Genet. 19:423-463, 1985),degenerate oligonucleotide-directed (Hill et al., Method Enzymology,155:558-568, 1987), region-specific (Myers et al., Science, 229:242-246,1985; Derbyshire et al., Gene, 46:145, 1986; Ner et al., DNA, 7:127,1988), linker-scanning (McKnight and Kingsbury, Science, 217:316-324,1982), directed using PCR, recursive ensemble mutagenesis (Arkin andYourvan, Proc. Natl. Acad. Sci., 89:7811-7815, 1992), random mutagenesis(e.g., U.S. Pat. Nos. 5,096,815; 5,198,346; and 5,223,409),site-directed mutagenesis (e.g., Walder et al., Gene, 42:133, 1986;Bauer et al., Gene, 37:73, 1985; Craik, Bio Techniques, January 1985,12-19; Smith et al., Genetic Engineering: Principles and Methods, PlenumPress, 1981), phage display (e.g., Lowman et al., Biochem. 30:10832-10837, 1991; Ladner et al., U.S. Pat. No. 5,223,409; Huse, WIPOPublication WO 92/06204), etc. Desired sequences can also be produced bythe assembly of target sequences using mutually priming oligonucleotides(Uhlmann, Gene, 71:29-40, 1988). For directed mutagenesis methods,analysis of the three-dimensional structure of the polypeptide can beused to guide and facilitate making mutants which effect polypeptideactivity. Sites of substrate-enzyme interaction or other biologicalactivities can also be determined by analysis of crystal structure asdetermined by such techniques as nuclear magnetic resonance,crystallography or photoaffinity labeling. See, for example, de Vos etal., Science 255:306-312, 1992; Smith et al., J. Mol. Biol. 224:899-904,1992; Wlodaver et al., FEBS Lett. 309:59-64, 1992.

[0097] In addition, libraries of differentially-regulated genes andfragments thereof can be used for screening and selection of genevariants. For instance, a library of coding sequences can be generatedby treating a double-stranded DNA with a nuclease under conditions wherethe nicking occurs, e.g., only once per molecule, denaturing thedouble-stranded DNA, renaturing it to for double-stranded DNA that caninclude sense/antisense pairs from different nicked products, removingsingle-stranded portions from reformed duplexes by treatment with S1nuclease, and ligating the resulting DNAs into an expression vecore. Bythis method, expression libraries can be made comprising “mutagenized”differentially-regulated genes. The entire coding sequence or partsthereof can be used.

[0098] Polynucleotide Expression, Polypeptides Produced Thereby, andSpecific-Binding Partners Thereto.

[0099] A polynucleotide according to the present invention can beexpressed in a variety of different systems, in vitro and in vivo,according to the desired purpose. For example, a polynucleotide can beinserted into an expression vector, introduced into a desired host, andcultured under conditions effective to achieve expression of apolypeptide coded for by the polynucleotide, to search for specificbinding partners. Effective conditions include any culture conditionswhich are suitable for achieving production of the polypeptide by thehost cell, including effective temperatures, pH, medium, additives tothe media in which the host cell is cultured (e.g., additives whichamplify or induce expression such as butyrate, or methotrexate if thecoding polynucleotide is adjacent to a dhfr gene), cycloheximide, celldensities, culture dishes, etc. A polynucleotide can be introduced intothe cell by any effective method including, e.g., naked DNA, calciumphosphate precipitation, electroporation, injection, DEAE-Dextranmediated transfection, fusion with liposomes, association with agentswhich enhance its uptake into cells, viral transfection. A cell intowhich a polynucleotide of the present invention has been introduced is atransformed host cell. The polynucleotide can be extrachromosomal orintegrated into a chromosome(s) of the host cell. It can be stable ortransient. An expression vector is selected for its compatibility withthe host cell. Host cells include, mammalian cells, e.g., COS, CV1, BHK,CHO, HeLa, LTK, NIH 3T3, PC-3 (CRL-1435), LNCaP (CRL-1740), CA-HPV-10(CRL-2220), PZ-HPV-7 (CRL-2221), MDA-PCa 2b (CRL-2422), 22Rv1 (CRL2505),NCI-H660 (CRL-5813), HS 804.sk (CRL-7535), LNCaP-FGF (CRL-10995), RWPE-1(CRL-11609), RWPE-2 (CRL-11610), PWR-1E (CRL 11611), rat MAT-Ly-LuB-2(CRL-2376),and other primary and established prostate and prostatecancer cell lines, insect cells, such as Sf9 (S. frugipeda) andDrosophila, bacteria, such as E. coli, Streptococcus, bacillus, yeast,such as Sacharomyces, S. cerevisiae, fungal cells, plant cells,embryonic or adult stem cells (e.g., mammalian, such as mouse or human).

[0100] Expression control sequences are similarly selected for hostcompatibility and a desired purpose, e.g., high copy number, highamounts, induction, amplification, controlled expression. Othersequences which can be employed include enhancers such as from SV40,CMV, RSV, inducible promoters, cell-type specific elements, or sequenceswhich allow selective or specific cell expression. Promoters that can beused to drive its expression, include, e.g., the endogenous promoter,MMTV, SV40, trp, lac, tac, or T7 promoters for bacterial hosts; or alphafactor, alcohol oxidase, or PGH promoters for yeast. RNA promoters canbe used to produced RNA transcripts, such as T7 or SP6. See, e.g.,Melton et al., Polynucleotide Res., 12(18):7035-7056, 1984; Dunn andStudier. J. Mol. Bio., 166:477-435, 1984; U.S. Pat. No. 5,891,636;Studier et al., Gene Expression Technology, Methods in Enzymology,85:60-89, 1987. In addition, as discussed above, translational signals(including in-frame insertions) can be included.

[0101] When a polynucleotide is expressed as a heterologous gene in atransfected cell line, the gene is introduced into a cell as describedabove, under effective conditions in which the gene is expressed. Theterm “heterologous” means that the gene has been introduced into thecell line by the “hand-of-man.” Introduction of a gene into a cell lineis discussed above. The transfected (or transformed) cell expressing thegene can be lysed or the cell line can be used intact.

[0102] For expression and other purposes, a polynucleotide can containcodons found in a naturally-occurring gene, transcript, or cDNA, forexample, e.g., as set forth in SEQ ID NOS 1, 3, 4, 6, 8, 10, 12, 14, 16,18, 20, 22, 24, 26, 28, and 30, or it can contain degenerate codonscoding for the same amino acid sequences. For instance, it may bedesirable to change the codons in the sequence to optimize the sequencefor expression in a desired host. See, e.g., U.S. Pat. Nos. 5,567,600and 5,567,862.

[0103] A polypeptide according to the present invention can be recoveredfrom natural sources, transformed host cells (culture medium or cells)according to the usual methods, including, detergent extraction (e.g.,non-ionic detergent, Triton X-100, CHAPS, octylglucoside, IgepalCA-630), ammonium sulfate or ethanol precipitation, acid extraction,anion or cation exchange chromatography, phosphocellulosechromatography, hydrophobic interaction chromatography, hydroxyapatitechromatography, lectin chromatography, gel electrophoresis. Proteinrefolding steps can be used, as necessary, in completing theconfiguration of the mature protein. Finally, high performance liquidchromatography (HPLC) can be employed for purification steps. Anotherapproach is express the polypeptide recombinantly with an affinity tag(Flag epitope, HA epitope, myc epitope, 6xHis, maltose binding protein,chitinase, etc) and then purify by anti-tag antibody-conjugated affinitychromatography.

[0104] The present invention also relates to antibodies, and otherspecific-binding partners, which are specific for polypeptides encodedby polynucleotides of the present invention. Antibodies, e.g.,polyclonal, monoclonal, recombinant, chimeric, humanized, single-chain,Fab, and fragments thereof, can be prepared according to any desiredmethod. See, also, screening recombinant immunoglobulin libraries (e.g.,Orlandi et al., Proc. Natl. Acad. Sci., 86:3833-3837, 1989; Huse et al.,Science, 256:1275-1281, 1989); in vitro stimulation of lymphocytepopulations; Winter and Milstein, Nature, 349: 293-299, 1991. Theantibodies can be IgM, IgG, subtypes, IgG2a, IgG1, etc. Antibodies, andimmune responses, can also be generated by administering naked DNA See,e.g., U.S. Pat. Nos. 5,703,055; 5,589,466; 5,580,859. Antibodies can beused from any source, including, goat, rabbit, mouse, chicken (e.g.,IgY; see, Duan, W0/029444 for methods of making antibodies in avianhosts, and harvesting the antibodies from the eggs). An antibodyspecific for a polypeptide means that the antibody recognizes a definedsequence of amino acids within or including the polypeptide. Otherspecific binding partners include, e.g., aptamers and PNA, can beprepared against specific epitopes or domains of differentiallyregulated genes.

[0105] The preparation of polyclonal antibodies is well-known to thoseskilled in the art. See, for example, Green et al., Production ofPolyclonal Antisera, in IMMUNOCHEMICAL PROTOCOLS (Manson, ed.), pages1-5 (Humana Press 1992); Coligan et al., Production of PolyclonalAntisera in Rabbits, Rats, Mice and Hamsters, in CURRENT PROTOCOLS INIMMUNOLOGY, section 2.4.1 (1992). The preparation of monoclonalantibodies likewise is conventional. See, for example, Kohler &Milstein, Nature 256:495 (1975); Coligan et al., sections 2.5.1-2.6.7;and Harlow et al., ANTIBODIES: A LABORATORY MANUAL, page 726 (ColdSpring Harbor Pub. 1988).

[0106] Antibodies can also be humanized, e.g., where they are to be usedtherapeutically. Humanized monoclonal antibodies are produced bytransferring mouse complementarity determining regions from heavy andlight variable chains of the mouse immunoglobulin into a human variabledomain, and then substituting human residues in the framework regions ofthe murine counterparts. The use of antibody components derived fromhumanized monoclonal antibodies obviates potential problems associatedwith the immunogenicity of murine constant regions. General techniquesfor cloning murine immunoglobulin variable domains are described, forexample, by Orlandi et al., Proc. Nat'l Acad. Sci. USA 86:3833 (1989),which is hereby incorporated in its entirety by reference. Techniquesfor producing humanized monoclonal antibodies are described, forexample, in U.S. Pat. No. 6,054,297, Jones et al., Nature 321: 522(1986); Riechmann et al., Nature 332: 323 (1988); Verhoeyen et al.,Science 239: 1534 (1988); Carter et al., Proc. Nat'l Acad. Sci. USA 89:4285 (1992); Sandhu, Crit. Rev. Biotech. 12: 437 (1992); and Singer etal., J. Immunol. 150: 2844 (1993).

[0107] Antibodies of the invention also may be derived from humanantibody fragments isolated from a combinatorial immunoglobulin library.See, for example, Barbas et al., METHODS: A COMPANION TO METHODS INENZYMOLOGY, VOL. 2, page 119 (1991); Winter et al., Ann. Rev. Immunol.12: 433 (1994). Cloning and expression vectors that are useful forproducing a human immunoglobulin phage library can be obtainedcommercially, for example, from STRATAGENE Cloning Systems (La Jolla,Calif.).

[0108] In addition, antibodies of the present invention may be derivedfrom a human monoclonal antibody. Such antibodies are obtained fromtransgenic mice that have been “engineered” to produce specific humanantibodies in response to antigenic challenge. In this technique,elements of the human heavy and light chain loci are introduced intostrains of mice derived from embryonic stem cell lines that containtargeted disruptions of the endogenous heavy and light chain loci. Thetransgenic mice can synthesize human antibodies specific for humanantigens and can be used to produce human antibody-secreting hybridomas.Methods for obtaining human antibodies from transgenic mice aredescribed, e.g., in Green et al., Nature Genet. 7:13 (1994); Lonberg etal., Nature 368:856 (1994); and Taylor et al., Int. Immunol. 6:579(1994).

[0109] Antibody fragments of the present invention can be prepared byproteolytic hydrolysis of the antibody or by expression in E. coli ofnucleic acid encoding the fragment. Antibody fragments can be obtainedby pepsin or papain digestion of whole antibodies by conventionalmethods. For example, antibody fragments can be produced by enzymaticcleavage of antibodies with pepsin to provide a 5S fragment denotedF(ab′).sub.2. This fragment can be further cleaved using a thiolreducing agent, and optionally a blocking group for the sulfhydrylgroups resulting from cleavage of disulfide linkages, to produce 3.5SFab′ monovalent fragments. Alternatively, an enzymatic cleavage usingpepsin produces two monovalent Fab′ fragments and an Fc fragmentdirectly. These methods are described, for example, by Goldenberg, U.S.Pat. No. 4,036,945 and No. 4,331,647, and references contained therein.These patents are hereby incorporated in their entireties by reference.See also Nisoiihoff et al., Arch. Biochem. Biophys. 89:230 (1960);Porter, Biochem. J. 73:119 (1959); Edelman et al, METHODS IN ENZYMOLOGY,VOL. 1, page 422 (Academic Press 1967); and Coligan et al. at sections2.8.1-2.8.10 and 2.10.1-2.10.4.

[0110] Other methods of cleaving antibodies, such as separation of heavychains to form monovalent light-heavy chain fragments, further cleavageof fragments, or other enzymatic, chemical, or genetic techniques canalso be used. For example, Fv fragments comprise an association ofV.sub.H and V.sub.L chains. This association may be noncovalent, asdescribed in Inbar et al., Proc. Nat'l Acad. Sci. USA 69:2659 (1972).Alternatively, the variable chains can be linked by an intermoleculardisulfide bond or cross-linked by chemicals such as glutaraldehyde. See,e.g., Sandhu, supra. Preferably, the Fv fragments comprise V.sub.H andV.sub.L chains connected by a peptide linker. These single-chain antigenbinding proteins (sFv) are prepared by constructing a structural genecomprising nucleic acid sequences encoding the V.sub.H and V.sub.Ldomains connected by an oligonucleotide. The structural gene is insertedinto an expression vector, which is subsequently introduced into a hostcell such as E. coli. The recombinant host cells synthesize a singlepolypeptide chain with a linker peptide bridging the two V domains.Methods for producing sFvs are described, for example, by Whitlow etal., METHODS: A COMPANION TO METHODS IN ENZYMOLOGY, VOL. 2, page 97(1991); Bird etal., Science 242:423-426 (1988); Ladneret al., U.S. Pat.No. 4,946,778; Pack et al., Bio/Technology 11: 1271-77 (1993); andSandhu, supra.

[0111] Another form of an antibody fragment is a peptide coding for asingle complementarity-determining region (CDR). CDR peptides (“minimalrecognition units”) can be obtained by constructing genes encoding theCDR of an antibody of interest. Such genes are prepared, for example, byusing the polymerase chain reaction to synthesize the variable regionfrom RNA of antibody-producing cells. See, for example, Larrick et al.,METHODS: A COMPANION TO METHODS IN ENZYMOLOGY, VOL. 2, page 106 (1991).

[0112] The term “antibody” as used herein includes intact molecules aswell as fragments thereof, such as Fab, F(ab′)2, and Fv which arecapable of binding to an epitopic determinant present in Bin1polypeptide. Such antibody fragments retain some ability to selectivelybind with its antigen or receptor. The term “epitope” refers to anantigenic determinant on an antigen to which the paratope of an antibodybinds. Epitopic determinants usually consist of chemically activesurface groupings of molecules such as amino acids or sugar side chainsand usually have specific three dimensional structural characteristics,as well as specific charge characteristics. Antibodies can be preparedagainst specific epitopes or polypeptide domains.

[0113] Antibodies which bind to a differentially-regulated polypeptideof the present invention can be prepared using an intact polypeptide orfragments containing small peptides of interest as the immunizingantigen. For example, it may be desirable to produce antibodies thatspecifically bind to the N- or C-terminal domains of said polypeptide.The polypeptide or peptide used to immunize an animal which is derivedfrom translated CDNA or chemically synthesized which can be conjugatedto a carrier protein, if desired. Such commonly used carriers which arechemically coupled to the immunizing peptide include keyhole limpethemocyanin (KLH), thyroglobulin, bovine serum albumin (BSA), and tetanustoxoid.

[0114] Polyclonal or monoclonal antibodies can be further purified, forexample, by binding to and elution from a matrix to which thepolypeptide or a peptide to which the antibodies were raised is bound.Those of skill in the art will know of various techniques common in theimmunology arts for purification and/or concentration of polyclonalantibodies, as well as monoclonal antibodies (See for example, Coligan,et al., Unit 9, Current Protocols in Immunology, Wiley Interscience,1994, incorporated by reference).

[0115] Anti-idiotype technology can also be used to produce inventionmonoclonal antibodies which mimic an epitope. For example, ananti-idiotypic monoclonal antibody made to a first monoclonal antibodywill have a binding domain in the hypervariable region which is the“image” of the epitope bound by the first monoclonal antibody.

[0116] Methods of Detecting Polypeptides

[0117] Polypeptides coded for by a differentially-regulated gene of thepresent invention can be detected, visualized, determined, quantitated,etc. according to any effective method. useful methods include, e.g.,but are not limited to, immunoassays, RIA (radioimmunassay), ELISA,(enzyme-linked-immunosorbent assay), immunoflourescence, flow cytometry,histology, electron microscopy, light microscopy, in situ assays,immunoprecipitation, Western blot, etc.

[0118] Immunoassays may be carried in liquid or on biological support.For instance, a sample (e.g., blood, stool, urine, cells, tissue, bodyfluids, etc.) can be brought in contact with and immobilized onto asolid phase support or carrier such as nitrocellulose, or other solidsupport that is capable of immobilizing cells, cell particles or solubleproteins. The support may then be washed with suitable buffers followedby treatment with the detectably labeled differentially-regulated genespecific antibody. The solid phase support can then be washed with abuffer a second time to remove unbound antibody. The amount of boundlabel on solid support may then be detected by conventional means.

[0119] A “solid phase support or carrier” includes any support capableof binding an antigen, antibody, or other specific binding partner.Supports or carriers include glass, polystyrene, polypropylene,polyethylene, dextran, nylon, amylases, natural and modified celluloses,polyacrylamides, and magnetite. A support material can have anystructural or physical configuration. Thus, the support configurationmay be spherical, as in a bead, or cylindrical, as in the inside surfaceof a test tube, or the external surface of a rod. Alternatively, thesurface may be flat such as a sheet, test strip, etc. Preferred supportsinclude polystyrene beads

[0120] One of the many ways in which gene peptide-specific antibody canbe detectably labeled is by linking it to an enzyme and using it in anenzyme immunoassay (EIA). See, e.g., Voller, A., “The Enzyme LinkedImmunosorbent Assay (ELISA),” 1978, Diagnostic Horizons 2, 1-7,Microbiological Associates Quarterly Publication, Walkersville, Md.);Voller, A. et al., 1978, J. Clin. Pathol. 31, 507-520; Butler, J. E.,1981, Meth. Enzymol. 73, 482-523; Maggio, E. (ed.), 1980, EnzymeImmunoassay, CRC Press, Boca Raton, Fla. The enzyme which is bound tothe antibody will react with an appropriate substrate, preferably achromogenic substrate, in such a manner as to produce a chemical moietythat can be detected, for example, by spectrophotometric, fluorimetricor by visual means. Enzymes that can be used to detectably label theantibody include, but are not limited to, malate dehydrogenase,staphylococcal nuclease, delta-5-steroid isomerase, yeast alcoholdehydrogenase, .alpha.-glycerophosphate, dehydrogenase, triose phosphateisomerase, horseradish peroxidase, alkaline phosphatase, asparaginase,glucose oxidase, .beta.-galactosidase, ribonuclease, urease, catalase,glucose-6-phosphate dehydrogenase, glucoamylase andacetylcholinesterase. The detection can be accomplished by colorimetricmethods that employ a chromogenic substrate for the enzyme. Detectionmay also be accomplished by visual comparison of the extent of enzymaticreaction of a substrate in comparison with similarly prepared standards.

[0121] Detection may also be accomplished using any of a variety ofother immunoassays. For example, by radioactively labeling theantibodies or antibody fragments, it is possible to detectdifferentially-regulated peptides through the use of a radioimmunoassay(RIA). See, e.g., Weintraub, B., Principles of Radioimmunoassays,Seventh Training Course on Radioligand Assay Techniques, The EndocrineSociety, March, 1986. The radioactive isotope can be detected by suchmeans as the use of a gamma counter or a scintillation counter or byautoradiography.

[0122] It is also possible to label the antibody with a fluorescentcompound. When the fluorescently labeled antibody is exposed to light ofthe proper wave length, its presence can then be detected due tofluorescence. Among the most commonly used fluorescent labelingcompounds are fluorescein isothiocyanate, rhodamine, phycoerythrin,phycocyanin, allophycocyanin, o-phthaldehyde and fluorescamine. Theantibody can also be detectably labeled using fluorescence emittingmetals such as those in the lanthanide series. These metals can beattached to the antibody using such metal chelating groups asdiethylenetriaminepentacetic acid (DTPA) or ethylenediaminetetraaceticacid (EDTA).

[0123] The antibody also can be detectably labeled by coupling it to achemiluminescent compound. The presence of the chemiluminescent-taggedantibody is then determined by detecting the presence of luminescencethat arises during the course of a chemical reaction. Examples of usefulchemiluminescent labeling compounds are luminol, isoluminol, theromaticacridinium ester, imidazole, acridinium salt and oxalate ester.

[0124] Likewise, a bioluminescent compound may be used to label theantibody of the present invention. Bioluminescence is a type ofchemiluminesccnce found in biological systems in which a catalyticprotein increases the efficiency of the chemiluminescent reaction. Thepresence of a bioluminescent protein is determined by detecting thepresence of luminescence. Important bioluminescent compounds forpurposes of labeling are luciferin, luciferase and aequorin.

[0125] Tissue and Disease

[0126] The prostate is a secretory organ surrounding the neck of thebladder and urethra. Its primary function is to produce fluids and othermaterials necessary for sperm transport and maintenance. Structurally,it has both glandular and nonglandular components. The glandularcomponent is predominantly comprised of ducts and acini responsible forthe production and transport prostatic fluids. Epithelial cells are themain identifiable cell found in these regions, primarily of the basaland secretory types, but also endocrine-paracrine and transitionalepithelial. The non-glandular component contains the capsular and muscletissues, which, respectively, hold the organ together and function influid discharge. See, e.g., Histology for Pathologists, Sternberg, S.S., editor, Raven Press, NY, 1992, Chapter 40.

[0127] The major diseases of the prostate include, e.g., prostatichyperplasia (BPH), prostatitis, and prostate cancer (e.g., prostaticadenocarcinoma). BPH is a benign, proliferative disease of the prostaticepithelial cells. While it may cause urinary tract obstruction in somepatients, for the most part, it is generally asymptomatic. Prostatecancer, on the other hand, is, the most common form of cancer in whitemales in the United States, occurring predominantly in males over age50. The prevalence of prostate diseases, such as prostate cancer, hasmade the discovery of prostate selective markers and gene expressionpatterns of great importance.

[0128] The most common scale of assessing prostate pathology is theGleason grading system. See, e.g., Bostwick, Am. J. Clin. Path., 102:s38-s56, 1994. Once the cancer is identified, staging can assess thesize, location, and extent of the cancer. Several different stagingscales are commonly used, including stages A-D, andTumor-Nodes-Metastases (TNM). For treatment, diagnosis, staging, etc.,of prostate conditions, methods can be carried out analogously to, andin combination with, U.S. Pat. Nos. 6,107,090; 6,057,116; 6,034,218;6,004,267; 5,919,638; 5,882,864; 5,763,202; 5,747,264; 5,688,649;5,552,277.

[0129] In addition, the present invention relates to methods ofassessing a therapeutic or preventative intervention in a subject havinga prostate cancer, comprising, e.g., detecting the expression levels ofdifferentially-regulated target genes, wherein the target genes comprisea gene which is represented by a sequence selected from Table 1, or, agene represented by a sequence having 90% sequence identity or more to asequence selected from Table 1. By “therapeutic or preventativeintervention,” it is meant, e.g., a drug administered a patient,surgery, radiation, chemotherapy, and other measures taken to prevent acancer or treat a cancer.

[0130] Grading, Staging, Comparing, Assessing, Methods and Compositions

[0131] The present invention also relates to methods and compositionsfor staging and grading cancers. As already defined, staging relates todetermining the extent of a cancer's spread, including its size and thedegree to which other tissues, such as lymph nodes are involved in thecancer. Grading refers to the degree of a cell's retention of thecharacteristics of the tissue of its origin. A lower grade cancercomprises tumor cells that more closely resemble normal cells than amedium or higher grade cancer. Grading can be a useful diagnostic andprognostic tool. Higher grade cancers usually behave more aggressivelythan lower grade cancers. Thus, knowledge of the cancer grade, as wellas its stage, can be a significant factor in the choice of theappropriate therapeutic intervention for the particular patient, e.g.,surgery, radiation, chemotherapy, etc. Staging and grading can also beused in conjunction with a therapy to assess its efficacy, to determineprognosis, to determine effective dosages, etc.

[0132] Various methods of staging and grading cancers can be employed inaccordance with the present invention. A “cell expression profile” or“cell expression fingerprint” is a representation of the expression ofvarious different genes in a given cell or sample comprising cells.These cell expression profiles can be useful as reference standards. Thecell expression fingerprints can be used alone for grading, or incombination with other grading methods.

[0133] The present invention also relates to methods and compositionsfor diagnosing a prostate cancer, or determining susceptibility to aprostate cancer, using polynucleotides, polypeptides, andspecific-binding partners of the present invention to detect, assess,determine, etc., differentially-regulated genes of the presentinvention. In such methods, the gene can serve as a marker for prostatecancer, e.g., where the gene, when mutant, is a direct cause of theprostate cancer; where the gene is affected by another gene(s) which isdirectly responsible for the prostate cancer, e.g., when the gene ispart of the same signaling pathway as the directly responsible gene;and, where the gene is chromosomally linked to the gene(s) directlyresponsible for the prostate cancer, and segregates with it. Many othersituations are possible. To detect, assess, determine, etc., a probespecific for the gene can be employed as described above and below. Anymethod of detecting and/or assessing the gene can be used, includingdetecting expression of the gene using polynucleotides, antibodies, orother specific-binding partners.

[0134] The present invention relates to methods of diagnosing a disorderassociated with prostate cancer, or determining a subject'ssusceptibility to such prostate cancer, comprising, e.g., assessing theexpression of a differentially-regulated gene in a tissue samplecomprising tissue or cells suspected of having a prostate cancer (e.g.,where the sample comprises prostate). The phrase “diagnosing” indicatesthat it is determined whether the sample has prostate cancer.“Determining a subject's susceptibility to a prostate cancer” indicatesthat the subject is assessed for whether s/he is predisposed to get sucha disease or disorder, where the predisposition is indicated by abnormalexpression of the gene (e.g., gene mutation, gene expression pattern isnot normal, etc.). Predisposition or susceptibility to a disease mayresult when a such disease is influenced by epigenetic, environmental,etc., factors. This includes prenatal screening where samples from thefetus or embryo (e.g., via amniocentesis or CV sampling) are analyzedfor the expression of the genes.

[0135] By the phrase “assessing expression of a differentially-regulatedgene,” it is meant that the functional status of the gene is evaluated.This includes, but is not limited to, measuring expression levels ofsaid gene, determining the genomic structure of said gene, determiningthe mRNA structure of transcripts from said gene, or measuring theexpression levels of polypeptide coded for by said gene. Thus, the term“assessing expression” includes evaluating the all aspects of thetranscriptional and translational machinery of the gene. For instance,if a promoter defect causes, or is suspected of causing, the disorder,then a sample can be evaluated (i.e., “assessed”) by looking (e.g.,sequencing or restriction mapping) at the promoter sequence in the gene,by detecting transcription products (e.g., RNA), by detectingtranslation product (e.g., polypeptide). Any measure of whether the geneis functional can be used, including, polypeptide, polynucleotide, andfunctional assays for the gene's biological activity.

[0136] In making the assessment, it can be useful to compare the resultsto a normal gene, e.g., a gene which is not associated with thedisorder. The nature of the comparison can be determined routinely,depending upon how the assessing is accomplished. If, for example, themRNA levels of a sample is detected, then the mRNA levels of a normalcan serve as a comparison, or a gene which is known not to be affectedby the disorder. Methods of detecting mRNA are well known, and discussedabove, e.g., but not limited to, Northern blot analysis, polymerasechain reaction (PCR), reverse transcriptase PCR, RACE PCR, etc.Similarly, if polypeptide production is used to evaluate the gene, thenthe polypeptide in a normal tissue sample can be used as a comparison,or, polypeptide from a different gene whose expression is known not tobe affected by the disorder. These are only examples of how such amethod could be carried out.

[0137] Assessing the effects of therapeutic and preventativeinterventions (e.g., administration of a drug, chemotherapy, radiation,etc.) on prostate cancer is a major effort in drug discovery, clinicalmedicine, and phanmacogenomics. The evaluation of therapeutic andpreventative measures, whether experimental or already in clinical use,has broad applicability, e.g., in clinical trials, for monitoring thestatus of a patient, for analyzing and assessing animal models, and inany scenario involving cancer treatment and prevention. Analyzing theexpression profiles of polynucleotides of the present invention can beutilized as a parameter by which interventions are judged and measured.Treatment of a disorder can change the expression profile in some mannerwhich is prognostic or indicative of the drug's effect on it. Changes inthe profile can indicate, e.g., drug toxicity, return to a normal level,etc. Accordingly, the present invention also relates to methods ofmonitoring or assessing a therapeutic or preventative measure (e.g.,chemotherapy, radiation, anti-neoplastic drugs, antibodies, etc.) in asubject having prostate cancer, or, susceptible to such a disorder,comprising, e.g., detecting the expression levels of one or moredifferentially-regulated genes of the present invention. A subject canbe a cell-based assay system, non-human animal model, human patient,etc. Detecting can be accomplished as described for the methods aboveand below. By “therapeutic or preventative intervention,” it is meant,e.g., a drug administered to a patient, surgery, radiation,chemotherapy, and other measures taken to prevent, treat, or diagnoseprostate cancer.

[0138] Expression can be assessed in any sample comprising any tissue orcell type, body fluid, etc., as discussed for other methods of thepresent invention, including cells from prostate can be used, or cellsderived from prostate. By the phrase “cells derived from prostate,” itis meant that the derived cells originate from prostate, e.g., whenmetastasis from a primary tumor site has occurred, when aprogenitor-type or pluripotent cell gives rise to other cells, etc.

[0139] The present invention also relates to methods of using bindingpartners for differentially-regulated genes, such as antibodies, todeliver active agents to the prostate for a variety of differentpurposes, including, e.g., for diagnostic, therapeutic (e.g., to treatcancer), and research purposes. Methods can involve delivering oradministering an active agent to the prostate, comprising, e.g.,administering to a subject in need thereof, an effective amount of anactive agent coupled to a binding partner specific for aidfferentially-regulated gene polypeptide, wherein said binding partneris effective to deliver said active agent specifically to prostate.

[0140] Any type of active agent can be used in combination with thebinding partner, including, therapeutic, cytotoxic, cytostatic,chemotherapeutic, anti-neoplastic, anti-proliferative, anti-biotic,etc., agents. A chemotherapeutic agent can be, e.g., DNA-interactiveagent, alkylating agent, antimetabolite, tubulin-interactive agent,hormonal agent, hydroxyurea, Cisplatin, Cyclophosphamide, Altretamine,Bleomycin, Dactinomycin, Doxorubicin, Etoposide, Teniposide, paclitaxel,cytoxan, 2-methoxycarbonylaminobenzimidazole, Plicamycin, Methotrexate,Fluorouracil, Fluorodeoxyuridin, CB3717, Azacitidine, Floxuridine,Mercapyopurine, 6-Thioguanine, Pentostatin, Cytarabine, Fludarabine,etc. Agents can also be contrast agents useful in imaging technology,e.g., X-ray, CT, CAT, MRI, ultrasound, PET, SPECT, and scintographic.

[0141] An active agent can be associated in any manner with a bindingpartner which is effective to achieve its delivery specifically to thetarget. Specific delivery or targeting indicates that the agent isprovided to the prostate, without being substantially provided to othertissues. This is useful especially where an agent is toxic, and specifictargeting to the prostate enables the majority of the toxicity to beaimed at the prostate, with as small as possible effect on other tissuesin the body. The association of the active agent and the binding partner(“coupling) can be direct, e.g., through chemical bonds between thebinding partner and the agent, or, via a linking agent, or theassociation can be less direct, e.g., where the active agent is in aliposome, or other carrier, and the binding partner is associated withthe liposome surface. In such case, the binding partner can be orientedin such a way that it is able to bind to the gene product on prostatecell surface. Methods for delivery of DNA via a cell-surface receptor isdescribed, e.g., in U.S. Pat. No. 6,339,139.

[0142] Identifying Agent Methods

[0143] The present invention also relates to methods of identifyingagents, and the agents themselves, which modulate differentiallyregulated genes and gene products of the present invention. These agentscan be used to modulate the biological activity of the polypeptideencoded for the gene, or the gene, itself. Agents which regulate thegene or its product are useful in variety of different environments,including as medicinal agents to treat or prevent disorders associatedwith differentially regulated genes and as research reagents to modifythe function of tissues and cell.

[0144] Methods of identifying agents generally comprise steps in whichan agent is placed in contact with the gene, transcription product,translation product, or other target, and then a determination isperformed to assess whether the agent “modulates” the target. Thespecific method utilized will depend upon a number of factors,including, e.g., the target (i.e., is it the gene or polypeptide encodedby it), the environment (e.g., in vitro or in vivo), the composition ofthe agent, etc.

[0145] For modulating the expression of differentially-regulated genesof the present invention, a method can comprise, in any effective order,one or more of the following steps, e.g., contacting adifferentially-regulated gene (e.g., in a cell population) with a testagent under conditions effective for said test agent to modulate theexpression of said gene, and determining whether said test agentmodulates said gene. An agent can modulate expression of adifferentially-regulated gene at any level, including transcription,translation, and/or perdurance of the nucleic acid (e.g., degradation,stability, etc.) in the cell. For modulating the biological activity ofpolypeptides coded for by differentially-regulated genes, a method cancomprise, in any effective order, one or more of the following steps,e.g., contacting a polypeptide (e.g., in a cell, lysate, or isolated)with a test agent under conditions effective for said test agent tomodulate the biological activity of said polypeptide, and determiningwhether said test agent modulates said biological activity.

[0146] Contacting a differentially-regulated gene or polypeptide withthe test agent can be accomplished by any suitable method and/or meansthat places the agent in a position to functionally control expressionor biological activity of said gene or polypeptide present in thesample. Functional control indicates that the agent can exert itsphysiological effect on the gene or polypeptide through whatevermechanism it works. The choice of the method and/or means can dependupon the nature of the agent and the condition and type of environmentin which the gene or polypeptide is presented, e.g., lysate, isolated,or in a cell population (such as, in vivo, in vitro, organ explants,etc.). For instance, if the cell population is an in vitro cell culture,the agent can be contacted with the cells by adding it directly into theculture medium. If the agent cannot dissolve readily in an aqueousmedium, it can be incorporated into liposomes, or another lipophiliccarrier, and then administered to the cell culture. Contact can also befacilitated by incorporation of agent with carriers and deliverymolecules and complexes, by injection, by infusion, etc.

[0147] After the agent has been administered in such a way that it cangain access to the gene or polypeptide, it can be determined whether thetest agent modulates their expression or biological activity. Modulationcan be of any type, quality, or quantity, e.g., increase, facilitate,enhance, up-regulate, stimulate, activate, amplify, augment, induce,decrease, down-regulate, diminish, lessen, reduce, etc. The modulatoryquantity can also encompass any value, e.g., 1%, 5%, 10%, 50%, 75%,1-fold, 2-fold, 5-fold, 10-fold, 100-fold, etc. To modulate geneexpression means, e.g., that the test agent has an effect on itsexpression, e.g., to effect the amount of transcription, to effect RNAsplicing, to effect translation of the RNA into polypeptide, to effectRNA or polypeptide stability, to effect polyadenylation or otherprocessing of the RNA, to effect post-transcriptional orpost-translational processing, etc. To modulate biological activitymeans, e.g., that a functional activity of the polypeptide is changed incomparison to its normal activity in the absence of the agent. Thiseffect includes, increase, decrease, block, inhibit, enhance, etc.

[0148] A test agent can be of any molecular composition, e.g., chemicalcompounds, biomolecules, such as polypeptides, lipids, nucleic acids(e.g., antisense to a polynucleotide sequence selected from SEQ ID NOS1, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30),carbohydrates, antibodies, ribozymes, double-stranded RNA, aptamers,etc. For example, if a polypeptide to be modulated is a cell-surfacemolecule, a test agent can be an antibody that specifically recognizesit and, e.g., causes the polypeptide to be internalized, leading to itsdown regulation on the surface of the cell. Such an effect does not haveto be permanent, but can require the presence of the antibody tocontinue the down-regulatory effect. Antibodies can also be used tomodulate the biological activity a polypeptide in a lysate or othercell-free form. Antisense can also be used as test agents to modulategene expression.

[0149] Markers

[0150] The polynucleotides of the present invention can be used withother markers, especially prostate and prostate cancer markers toidentity, detect, stage, diagnosis, determine, prognosticate, treat,etc., tissue, diseases and conditions, etc, of the prostate. Markers canbe polynucleotides, polypeptides, antibodies, ligands, specific bindingpartners, etc.

[0151] A number of genes and gene products have been identified whichare associated with prostate cancer metastasis and/or progression, e.g.,PSA, KAI1 (shows decreased expression in metastatic cells; Dong et al.,Science, 268:884-6, 1995), D44 isoforms (differentially-regulated duringcarcinoma progression; Noordzij et al., Clin. Cancer Res., 3:805-15,1997), p53 (Effert et al., J. Urol., 150:257-61, 1993), Rb, CDKN2,E-cadherin, PTEN (Hamilton et al., Br. J. Cancer, 82:1671-6, 2000; Donget al., Clin. Cancer Res., 7:304-308, 2001), bc1-2, prostatic acidphosphatase (PAP), prostate specific membrane antigen (e.g., U.S. Pat.Nos. 5,538,866 and 6,107,090), Smad3 (e.g., Kang et al., Proc. Natl.Acad. Sci., 98:3018-3023, 2001), TGF-beta, and other oncogenes and tumorsuppressor genes. See, also, Myers and Grizzle, Eur. Urol., 30:153-166,1996, for other biomarkers associated with prostatic carcinoma, such asPCNA, p185-erbB-2, p180erbB-3, TAG-72, nm23-H1 and FASE. Such markerscan be used in combination with the methods of the present invention tofacilitate identifying, grading, staging, prognostication, etc, ofconditions and diseases of the prostate.

[0152] Therapeutics

[0153] Selective polynucleotides, polypeptides, and specific-bindingpartners thereto, can be utilized in therapeutic applications,especially to treat prostate cancer. Useful methods include, but are notlimited to, immunotherapy (e.g., using specific-binding partners topolypeptides), vaccination (e.g., using a selective polypeptide or anaked DNA encoding such polypeptide), protein or polypeptide replacementtherapy, gene therapy (e.g., germ-line correction, antisense), etc.

[0154] Various immunotherapeutic approaches can be used. For instance,unlabeled antibody that specifically recognizes a tissue-specificantigen can be used to stimulate the body to destroy or attack thecancer, to cause down-regulation, to produce complement-mediated lysis,to inhibit cell growth, etc., of target cells which display the antigen,e.g., analogously to how c-erbB-2 antibodies are used to treat breastcancer. In addition, antibody can be labeled or conjugated to enhanceits deleterious effect, e.g., with radionuclides and other energyemitting entitities, toxins, such as ricin, exotoxin A (ETA), anddiphtheria, cytotoxic or cytostatic agents, immunomodulators,chemotherapeutic agents, etc. See, e.g., U.S. Pat. No. 6,107,090.

[0155] An antibody or other specific-binding partner can be conjugatedto a second molecule, such as a cytotoxic agent, and used for targetingthe second molecule to a tissue-antigen positive cell (Vitetta, E. S. etal., 1993, Immunotoxin therapy, in DeVita, Jr., V. T. et al., eds,Cancer: Principles and Practice of Oncology, 4th ed., J. B. LippincottCo., Philadelphia, 2624-2636). Examples of cytotoxic agents include, butare not limited to, antimetabolites, alkylating agents, anthracyclines,antibiotics, anti-mitotic agents, radioisotopes and chemotherapeuticagents. Further examples of cytotoxic agents include, but are notlimited to ricin, doxorubicin, daunorubicin, taxol, ethidium bromide,mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine,dihydroxy anthracin dione, actinomycin D, 1-dehydrotestosterone,diptheria toxin, Pseudomonas exotoxin (PE) A, PE40, abrin, elongationfactor-2 and glucocorticoid. Techniques for conjugating therapeuticagents to antibodies are well.

[0156] In addition to immunotherapy, polynucleotides and polypeptidescan be used as targets for non-immunotherapeutic applications, e.g.,using compounds which interfere with function, expression (e.g.,antisense as a therapeutic agent), assembly, etc. RNA interference canbe used in vivtro and in vivo to silence differentially-expressed geneswhen its expression contributes to a disease (but also for otherpurposes, e.g., to identify the gene's function to change adevelopmental pathway of a cell, etc.). See, e.g., Sharp and Zamore,Science, 287:2431-2433, 2001; Grishok et al., Science, 287:2494, 2001.

[0157] Delivery of therapeutic agents can be achieved according to anyeffective method, including, liposomes, viruses, plasmid vectors,bacterial delivery systems, orally, systemically, etc. Therapeuticagents of the present invention can be administered in any form by anyeffective route, including, e.g., oral, parenteral, enteral,intraperitoneal, topical, transdermal (e.g., using any standard patch),ophthalmic, nasally, local, non-oral, such as aerosal, inhalation,subcutaneous, intramuscular, buccal, sublingual, rectal, vaginal,intra-arterial, and intrathecal, etc. They can be administered alone, orin combination with any ingredient(s), active or inactive.

[0158] In addition to therapeutics, per se, the present invention alsorelates to methods of treating prostate cancer showing alteredexpression of differentially-regulated genes, such as SEQ ID NOS 1-31,comprising, e.g., administering to a subject in need thereof atherapeutic agent which is effective for regulating expression of saidgenes and/or which is effective in treating said disease. The term“treating” is used conventionally, e.g., the management or care of asubject for the purpose of combating, alleviating, reducing, relieving,improving the condition of, etc., of a disease or disorder. By thephrase “altered expression,” it is meant that the disease is associatedwith a mutation in the gene, or any modification to the gene (orcorresponding product) which affects its normal function. Thus,expression of a differentially-regulated gene refers to, e.g.,transcription, translation, splicing, stability of the mRNA or proteinproduct, activity of the gene product, differential expression, etc.

[0159] Any agent which “treats” the disease can be used. Such an agentcan be one which regulates the expression of the gene. Expression refersto the same acts already mentioned, e.g. transcription, translation,splicing, stability of the mRNA or protein product, activity of the geneproduct, differential expression, etc. For instance, if the conditionwas a result of a complete deficiency of the gene product,administration of gene product to a patient would be said to treat thedisease and regulate the gene's expression. Many other possiblesituations are possible, e.g., where the gene is aberrantly expressed,and the therapeutic agent regulates the aberrant expression by restoringits normal expression pattern.

[0160] Antisense

[0161] Antisense polynucleotide (e.g., RNA) can also be prepared from apolynucleotide according to the present invention, preferably ananti-sense to a sequence of SEQ ID NOS 1, 3, 4, 6, 8, 10, 12, 14, 16,18, 20, 22, 24, 26, 28, and 30. Antisense polynucleotide can be used invarious ways, such as to regulate or modulate expression of thepolypeptides they encode, e.g., inhibit their expression, for in situhybridization, for therapeutic purposes, for making targeted mutations(in vivo, triplex, etc.) etc. For guidance on administering anddesigning anti-sense, see, e.g., U.S. Pat. Nos. 6,200,960, 6,200,807,6,197,584, 6,190,869, 6,190,661, 6,187,587, 6,168,950, 6,153,595,6,150,162, 6,133,246, 6,117,847, 6,096,722, 6,087,343, 6,040,296,6,005,095, 5,998,383, 5,994,230, 5,891,725, 5,885,970, and 5,840,708. Anantisense polynucleotides can be operably linked to an expressioncontrol sequence. A total length of about 35 bp can be used in cellculture with cationic liposomes to facilitate cellular uptake, but forin vivo use, preferably shorter oligonucleotides are administered, e.g.25 nucleotides.

[0162] Antisense polynucleotides can comprise modified,normaturally-occurring nucleotides and linkages between the nucleotides(e.g., modification of the phosphate-sugar backbone; methyl phosphonate,phosphorothioate, or phosphorodithioate linkages; and 2′-O-methyl ribosesugar units), e.g., to enhance in vivo or in vitro stability, to confernuclease resistance, to modulate uptake, to modulate cellulardistribution and compartmentalization, etc. Any effective nucleotide ormodification can be used, including those already mentioned, as known inthe art, etc., e.g., disclosed in U.S. Pat. Nos. 6,133,438; 6,127,533;6,124,445; 6,121,437; 5,218,103 (e.g., nucleoside thiophosphoramidites);4,973,679; Sproat et al., “2′-O-Methyloligoribonucleotides: synthesisand applications,” Oligonucleotides and Analogs A Practical Approach,Eckstein (ed.), IRL Press, Oxford, 1991, 49-86; Iribarren et al.,“2′O-Alkyl Oligoribonucleotides as Antisense Probes,” Proc. Natl. Acad.Sci. USA, 1990, 87, 7747-7751; Cotton et al., “2′-O-methyl, 2′-O-ethyloligoribonucleotides and phosphorothioate oligodeoxyribonucleotides asinhibitors of the in vitro U7 snRNP-dependent mRNA processing event,”Nucl. Acids Res., 1991, 19, 2629-2635.

[0163] Arrays

[0164] The present invention also relates to an ordered array ofpolynucleotide probes and specific-binding partners (e.g., antibodies)for detecting the expression of differentially-regulated genes in asample, comprising, one or more polynucleotide probes or specificbinding partners associated with a solid support, wherein each probe isspecific for said genes, and the probes comprise a nucleotide sequenceof SEQ ID NOS 1, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and30 which is specific for said gene, a nucleotide sequence havingsequence identity to SEQ ID NOS 1, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20,22, 24, 26, 28, and 30 which is specific for said gene orpolynucleotide, or complements thereto, or a specific-binding partnerwhich is specific for said genes.

[0165] The phrase “ordered array” indicates that the probes are arrangedin an identifiable or position-addressable pattern, e.g., such as thearrays disclosed in U.S. Pat. Nos. 6,156,501, 6,077,673, 6,054 ,270,5,723,320, 5,700,637, WO09919711, WO00023803. The probes are associatedwith the solid support in any effective way. For instance, the probescan be bound to the solid support, either by polymerizing the probes onthe substrate, or by attaching a probe to the substrate. Association canbe, covalent, electrostatic, noncovalent, hydrophobic, hydrophilic,noncovalent, coordination, adsorbed, absorbed, polar, etc. When fibersor hollow filaments are utilized for the array, the probes can fill thehollow orifice, be absorbed into the solid filament, be attached to thesurface of the orifice, etc. Probes can be of any effective size,sequence identity, composition, etc., as already discussed.

[0166] Ordered arrays can further comprise polynucleotide probes orspecific-binding partners which are specific for other genes, includinggenes specific for prostate or disorders associated with prostate.

[0167] Transgenic Animals

[0168] The present invention also relates to transgenic animalscomprising differentially-regulated genes of the present invention. Suchgenes, as discussed in more detail below, include, but are not limitedto, functionally-disrupted genes, mutated genes, ectopically orselectively-expressed genes, inducible or regulatable genes, etc. Thesetransgenic animals can be produced according to any suitable techniqueor method, including homologous recombination, mutagenesis (e.g., ENU,Rathkolb et al., Exp. Physiol., 85(6):635-644, 2000), and thetetracycline-regulated gene expression system (e.g., U.S. Pat. No.6,242,667). The term “gene” as used herein includes any part of a gene,i.e., regulatory sequences, promoters, enhancers, exons, introns, codingsequences, etc. The nucleic acid present in the construct or transgenecan be naturally-occurring wild-type, polymorphic, or mutated. When amouse or other mammal is used, the appropriate homolog can be used inplace of a human gene of the present invention.

[0169] Along these lines, polynucleotides of the present invention canbe used to create transgenic animals, e.g. a non-human animal,comprising at least one cell whose genome comprises a functionaldisruption of a differentially-regulated gene. By the phrases“functional disruption” or “functionally disrupted,” it is meant thatthe gene does not express a biologically-active product. It can besubstantially deficient in at least one functional activity coded for bythe gene. Expression of a polypeptide can be substantially absent, i.e.,essentially undetectable amounts are made. However, polypeptide can alsobe made, but which is deficient in activity, e.g., where only anamino-terminal portion of the gene product is produced.

[0170] The transgenic animal can comprise one or more cells. Whensubstantially all its cells contain the engineered gene, it can bereferred to as a transgenic animal “whose genome comprises” theengineered gene. This indicates that the endogenous gene loci of theanimal has been modified and substantially all cells contain suchmodification.

[0171] Functional disruption of the gene can be accomplished in anyeffective way, including, e.g., introduction of a stop codon into anypart of the coding sequence such that the resulting polypeptide isbiologically inactive (e.g., because it lacks a catalytic domain, aligand binding domain, etc.), introduction of a mutation into a promoteror other regulatory sequence that is effective to turn it off, or reducetranscription of the gene, insertion of an exogenous sequence into thegene which inactivates it (e.g., which disrupts the production of abiologically-active polypeptide or which disrupts the promoter or othertranscriptional machinery), deletion of sequences from the adifferentially-regulated gene, etc. Examples of transgenic animalshaving functionally disrupted genes are well known, e.g., as describedin U.S. Pat. Nos. 6,239,326, 6,225,525, 6,207,878, 6,194,633, 6,187,992,6,180,849, 6,177,610, 6,100,445, 6,087,555, 6,080,910, 6,069,297,6,060,642, 6,028,244, 6,013,858, 5,981,830, 5,866,760, 5,859,314,5,850,004, 5,817,912, 5,789,654, 5,777,195, and 5,569,824. A transgenicanimal which comprises the functional disruption can also be referred toas a “knock-out” animal, since the biological activity of its adifferentially-regulated gene has been “knocked-out.” Knock-outs can behomozygous or heterozygous.

[0172] For creating functional disrupted genes, and other genemutations, homologous recombination technology is of special interestsince it allows specific regions of the genome to be targeted. Usinghomologous recombination methods, genes can be specifically-inactivated,specific mutations can be introduced, and exogenous sequences can beintroduced at specific sites. These methods are well known in the art,e.g., as described in the patents above. See, also, Robertson, Biol.Reproduc., 44(2):238-245, 1991. Generally, the genetic engineering isperformed in an embryonic stem (ES) cell, or other pluripotent cell line(e.g., adult stem cells, EG cells), and that genetically-modified cell(or nucleus) is used to create a whole organism. Nuclear transfer can beused in combination with homologous recombination technologies.

[0173] For example, a differentially-regulated gene locus can bedisrupted in mouse ES cells using a positive-negative selection method(e.g., Mansour et al., Nature, 336:348-352, 1988). In this method, atargeting vector can be constructed which comprises a part of the geneto be targeted. A selectable marker, such as neomycin resistance genes,can be inserted into a a differentially-regulated gene exon present inthe targeting vector, disrupting it. When the vector recombines with theES cell genome, it disrupts the function of the gene. The presence inthe cell of the vector can be determined by expression of neomycinresistance. See, e.g., U.S. Pat. No. 6,239,326. Cells having at leastone functionally disrupted gene can be used to make chimeric andgermline animals, e.g., animals having somatic and/or germ cellscomprising the engineered gene. Homozygous knock-out animals can beobtained from breeding heterozygous knock-out animals. See, e.g., U.S.Pat. No. 6,225,525.

[0174] A transgenic animal, or animal cell, lacking one or morefunctional differentially-regulated genes can be useful in a variety ofapplications, including, as an animal model for cancer, for drugscreening assays, as a source of tissues deficient in said geneactivity, and any of the utilities mentioned in any issued U.S. Patenton transgenic animals, including, U.S. Pat. Nos. 6,239,326, 6,225,525,6,207,878, 6,194,633, 6,187,992, 6,180,849, 6,177,610, 6,100,445,6,087,555, 6,080,910, 6,069,297, 6,060,642, 6,028,244, 6,013,858,5,981,830, 5,866,760, 5,859,314, 5,850,004, 5,817,912, 5,789,654,5,777,195, and 5,569,824. Transgenic animals in accordance with thepresent invention can be susceptible to prostate cancers.

[0175] The present invention also relates to non-human, transgenicanimal whose genome comprises recombinant a differentially-regulatedgene nucleic acid operatively linked to an expression control sequenceeffective to express said coding sequence, e.g., in prostate. such atransgenic animal can also be referred to as a “knock-in” animal sincean exogenous gene has been introduced, stably, into its genome.

[0176] A recombinant a differentially-regulated gene nucleic acid refersto a gene which has been introduced into a target host cell andoptionally modified, such as cells derived from animals, plants,bacteria, yeast, etc. A recombinant a differentially-regulated geneincludes completely synthetic nucleic acid sequences, semi-syntheticnucleic acid sequences, sequences derived from natural sources, andchimeras thereof. “Operable linkage” has the meaning used through thespecification, i.e., placed in a functional relationship with anothernucleic acid. When a gene is operably linked to an expression controlsequence, as explained above, it indicates that the gene (e.g., codingsequence) is joined to the expression control sequence (e.g., promoter)in such a way that facilitates transcription and translation of thecoding sequence. As described above, the phrase “genome” indicates thatthe genome of the cell has been modified. In this case, the recombinanta differentially-regulated gene has been stably integrated into thegenome of the animal. The a differentially-regulated gene nucleic acidin operable linkage with the expression control sequence can also bereferred to as a construct or transgene.

[0177] Any expression control sequence can be used depending on thepurpose. For instance, if selective expression is desired, thenexpression control sequences which limit its expression can be selected.These include, e.g., tissue or cell-specific promoters, introns,enhancers, etc. For various methods of cell and tissue-specificexpression, see, e.g., U.S. Pat. Nos. 6,215,040, 6,210,736, and6,153,427. These also include the endogenous promoter, i.e., the codingsequence can be operably linked to its own promoter. Inducible andregulatable promoters can also be utilized.

[0178] The present invention also relates to a transgenic animal whichcontains a functionally disrupted and a transgene stably integrated intothe animals genome. Such an animal can be constructed using combinationsany of the above- and below-mentioned methods. Such animals have any ofthe aforementioned uses, including permitting the knock-out of thenormal gene and its replacement with a mutated gene. Such a transgenecan be integrated at the endogenous gene locus so that the functionaldisruption and “knock-in” are carried out in the same step.

[0179] In addition to the methods mentioned above, transgenic animalscan be prepared according to known methods, including, e.g., bypronuclear injection of recombinant genes into pronuclei of 1-cellembryos, incorporating an artificial yeast chromosome into embryonicstem cells, gene targeting methods, embryonic stem cell methodology,cloning methods, nuclear transfer methods. See, also, e.g., U.S. Pat.Nos. 4,736,866; 4,873,191; 4,873,316; 5,082,779; 5,304,489; 5,174,986;5,175,384; 5,175,385; 5,221,778; Gordon et al., Proc. Natl. Acad. Sci.,77:7380-7384, 1980; Palmiter et al., Cell, 41:343-345, 1985; Palmiter etal., Ann. Rev. Genet., 20:465-499, 1986; Askew et al., Mol. Cell. Bio.,13:4115-4124, 1993; Games et al. Nature, 373:523-527, 1995; Valanciusand Smithies, Mol. Cell. Bio., 11:1402-1408, 1991; Stacey et al., Mol.Cell. Bio., 14:1009-1016, 1994; Hasty et al., Nature, 350:243-246, 1995;Rubinstein et al., Nucl. Acid Res., 21:2613-2617,1993; Cibelli et al.,Science, 280:1256-1258, 1998. For guidance on recombinase excisionsystems, see, e.g., U.S. Pat. Nos. 5,626,159, 5,527,695, and 5,434,066.See also, Orban, P. C., et al., “Tissue- and Site-Specific DNARecombination in Transgenic Mice,” Proc. Natl. Acad. Sci. USA,89:6861-6865 (1992); O'Gorman, S., et al., “Recombinase-Mediated GeneActivation and Site-Specific Integration in Mammalian Cells,” Science,251:1351-1355 (1991); Sauer, B., et al., “Cre-stimulated recombinationat loxP-Containing DNA sequences placed into the mammalian genome,”Polynucleotides Research, 17(1):147-161 (1989); Gagneten, S. et al.(1997) Nucl. Acids Res. 25:3326-3331; Xiao and Weaver (1997) Nucl. AcidsRes. 25:2985-2991; Agah, R. et al. (1997) J. Clin. Invest. 100:169-179;Barlow, C. et al. (1997) Nucl. Acids Res. 25:2543-2545; Araki, K. et al.(1997) Nucl. Acids Res. 25:868-872; Mortensen, R. N. et al. (1992) Mol.Cell. Biol. 12:2391-2395 (G418 escalation method); Lakhlani, P. P. etal. (1997) Proc. Natl. Acad. Sci. USA 94:9950-9955 (“hit and run”);Westphal and Leder (1997) Curr. Biol. 7:530-533 (transposon-generated“knock-out” and “knock-in”); Templeton, N. S. et al. (1997) Gene Ther.4:700-709 (methods for efficient gene targeting, allowing for a highfrequency of homologous recombination events, e.g., without selectablemarkers); PCT International Publication WO 93/22443(functionally-disrupted).

[0180] A polynucleotide according to the present invention can beintroduced into any non-human animal, including a non-human mammal,mouse (Hogan et al., Manipulating the Mouse Embryo: A Laboratory Manual,Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1986), pig(Hammer et al., Nature, 315:343-345, 1985), sheep (Hammer et al.,Nature, 315:343-345, 1985), cattle, rat, or primate. See also, e.g.,Church, 1987, Trends in Biotech. 5:13-19; Clark et al., Trends inBiotech. 5:20-24, 1987); and DePamphilis et al., BioTechniques,6:662-680, 1988. Transgenic animals can be produced by the methodsdescribed in U.S. Pat. No. 5,994,618, and utilized for any of theutilities described therein.

[0181] Database

[0182] The present invention also relates to electronic forms ofpolynucleotides, polypeptides, etc., of the present invention, includingcomputer-readable medium (e.g., magnetic, optical, etc., stored in anysuitable format, such as flat files or hierarchical files) whichcomprise such sequences, or fragments thereof, e-commerce-related means,etc. Along these lines, the present invention relates to methods ofretrieving gene sequences from a computer-readable medium, comprising,one or more of the following steps in any effective order, e.g.,selecting a cell or gene expression profile, e.g., a profile thatspecifies that said gene is differentially expressed in prostate cancer,and retrieving said differentially expressed gene sequences, where thegene sequences consist of the genes represented by SEQ ID NOS 1-31.

[0183] A “gene expression profile” means the list of tissues, cells,etc., in which a defined gene is expressed (i.e, transcribed and/ortranslated). A “cell expression profile” means the genes which areexpressed in the particular cell type. The profile can be a list of thetissues in which the gene is expressed, but can include additionalinformation as well, including level of expression (e.g., a quantity ascompared or normalized to a control gene), and information on temporal(e.g., at what point in the cell-cycle or developmental program) andspatial expression. By the phrase “selecting a gene or cell expressionprofile,” it is meant that a user decides what type of gene or cellexpression pattern he is interested in retrieving, e.g., he may requirethat the gene is differentially expressed in a tissue, or he may requirethat the gene is not expressed in blood, but must be expressed inprostate cancer. Any pattern of expression preferences may be selected.The selecting can be performed by any effective method. In general,“selecting” refers to the process in which a user forms a query that isused to search a database of gene expression profiles. The step ofretrieving involves searching for results in a database that correspondto the query set forth in the selecting step. Any suitable algorithm canbe utilized to perform the search query, including algorithms that lookfor matches, or that perform optimization between query and data. Thedatabase is information that has been stored in an appropriate storagemedium, having a suitable computer-readable format. Once results areretrieved, they can be displayed in any suitable format, such as HTML.

[0184] For instance, the user may be interested in identifying genesthat are differentially expressed in a prostate cancer. He may not carewhether small amounts of expression occur in other tissues, as long assuch genes are not expressed in peripheral blood lymphocytes. A query isformed by the user to retrieve the set of genes from the database havingthe desired gene or cell expression profile. Once the query is inputtedinto the system, a search algorithm is used to interrogate the database,and retrieve results.

[0185] Advertising, Licensing, etc., Methods

[0186] The present invention also relates to methods of advertising,licensing, selling, purchasing, brokering, etc., genes, polynucleotides,specific-binding partners, antibodies, etc., of the present invention.Methods can comprises, e.g., displaying a differentially-regulated gene, a differentially-regulated gene polypeptide, or antibody specific fora differentially-regulated gene in a printed or computer-readable medium(e.g., on the Web or Internet), accepting an offer to purchase saidgene, polypeptide, or antibody.

[0187] Other

[0188] A polynucleotide, probe, polypeptide, antibody, specific-bindingpartner, etc., according to the present invention can be isolated. Theterm “isolated” means that the material is in a form in which it is notfound in its original environment or in nature, e.g., more concentrated,more purified, separated from component, etc. An isolated polynucleotideincludes, e.g., a polynucleotide having the sequenced separated from thechromosomal DNA found in a living animal, e.g., as the complete gene, atranscript, or a cDNA. This polynucleotide can be part of a vector orinserted into a chromosome (by specific gene-targeting or by randomintegration at a position other than its normal position) and still beisolated in that it is not in a form that is found in its naturalenvironment. A polynucleotide, polypeptide, etc., of the presentinvention can also be substantially purified. By substantially purified,it is meant that polynucleotide or polypeptide is separated and isessentially free from other polynucleotides or polypeptides, i.e., thepolynucleotide or polypeptide is the primary and active constituent. Apolynucleotide can also be a recombinant molecule. By “recombinant,” itis meant that the polynucleotide is an arrangement or form which doesnot occur in nature. For instance, a recombinant molecule comprising apromoter sequence would not encompass the naturally-occurring gene, butwould include the promoter operably linked to a coding sequence notassociated with it in nature, e.g., a reporter gene, or a truncation ofthe normal coding sequence.

[0189] The term “marker” is used herein to indicate a means fordetecting or labeling a target. A marker can be a polynucleotide(usually referred to as a “probe”), polypeptide (e.g., an antibodyconjugated to a detectable label), PNA, or any effective material.

[0190] The topic headings set forth above are meant as guidance wherecertain information can be found in the application, but are notintended to be the only source in the application where information onsuch topic can be found.

[0191] Reference Materials

[0192] For other aspects of the polynucleotides, reference is made tostandard textbooks of molecular biology. See, e.g., Hames et al.,Polynucleotide Hybridization, IL Press, 1985; Davis et al., BasicMethods in Molecular Biology, Elsevir Sciences Publishing, Inc., NewYork, 1986; Sambrook et al., Molecular Cloning, CSH Press, 1989; Howe,Gene Cloning and Manipulation, Cambridge University Press, 1995; Ausubelet al., Current Protocols in Molecular Biology, John Wiley & Sons, Inc.,1994-1998.

[0193] Without further elaboration, it is believed that one skilled inthe art can, using the preceding description, utilize the presentinvention to its fullest extent. The following preferred specificembodiments are, therefore, to be construed as merely illustrative, andnot limitative of the remainder of the disclosure in any way whatsoever.The entire disclosure of all applications, patents and publications,cited above and in the figures are hereby incorporated by reference intheir entirety. TABLE 1 GENE EXPRESSION LENGTH DOMAINS  1. PCP0405 DOWN1379  1. CUB domain: 93-209aa; (SEQ ID NO 1-2)  2. DSL domain:222-280aa;  3. Kelch domain: 480-531aa;  4. Kelch domain: 532-591aa;  5.PSI domain: 614-657aa;  6. PSI domain: 666-709aa;  7. CLECT domain:748-873aa;  8. PSI domain: 889-939aa;  9. PSI domain: 942-1012aa; 10.EGF-like domain: 1014-1057aa; 11. EGF-like domain: 1060-1106aa; 12.Transmembrane domain: 1230-1252aa.  2. PCP0454A DOWN 3863  1. Internalrepeat 2: 19-72; (SEQ ID NO 6-7)  2. Internal repeat 1: 71-135;  3.Internal repeat 2: 332-385;  4. Internal repeat 1: 488-554. PCP0454BDOWN 577  1. Internal repeat 1: 1-137; (SEQ ID NO 4-5)  2. AAA domain:241-408.  3. PCP0459 UP 715  1. Gag p10 domain: 1-89; (SEQ ID NO 8·9) 2. Gag p24 domain: 360-573,  3. ZnF C2HC domain: 592-608;  4. ZnF C2HCdomain: 629-645.  4. PC0177A UP 1744  1. Coiled coil: 646-685; (SEQ IDNO 10-11)  2. Coiled coil: 1469-1481;  3. Coiled coil: 1656-1684.PC0177B UP 1709  1. Coiled coil: 611-650; (SEQ ID NO 12-13)  2. Coiledcoil: 1434-1456;  3. Coiled coil: 1621-1649. PC0177C UP 1908  1. Coiledcoil: 611-650; (SEQ ID NO 14-15)  2. Coiled coil: 1434-1456;  3. Coiledcoil: 1621-1649. PC0177D UP 1309  1. Coiled coil: 611-650 (SEQ ID NO16-17)  5. PCP0557 UP 1593  1. HisKA: 565-620; (SEQ ID NO 18-19)  2.Coiled coil: 933-965;  3. Coiled coil: 1464-1491.  6. PCP0664 UP 112  1.Transmembrane: 4-26. (SEQ ID NO 20-21)  7. PCP0677 UP 89 No domainfound. (SEQ ID NO 22-23)  8. PCP0762 UP 221  1. SCAN domain 42-137 (SEQID NO 24-25)  9. PCP0806 UP 548  1. SCOP domain: 10-122 (SEQ ID NO26-27)  2. Coiled coil: 374-409 10. PCP0815A UP 1005  1. ZnF C2H2domain: 371-393; (SEQ ID NO 28-29)  2. ZnF C2H2 domain: 399-421;  3. ZnFC2H2 domain: 629-651;  4. ZnF C2H2 domain: 657-679;  5. ZnF C2H2 domain:689-711;  6. ZnF C2H2 domain: 909-931;  7. ZnF C2H2 domain: 9380961.PCP0815C UP 198 No domain found (SEQ ID NO 30-31)

[0194] TABLE 2 Clone ID Locus Diseases PCP0405 10q26 Cancers PCP04546q15 Amaurosis Congenita Of Leber V; Cardiomyopathy, Dilated, 1k(Cmd1k); Chorioretinal Atrophy, Progressive Bifocal; Macular Dystrophy,Retinal, 1, North Carolina Type (Mcdr1) PCP0459 22q11.21 Cancers PC017710p11.22 Diabetes PCP0577 Xq25-q26.3 Mental Retardation, X-Linked, WithShort Stature, Small Testes, Muscle Wasting, And Tremor; Hypertrichosis,Congenital Generalized (Htc2); Borjeson-Forssman-Lehmann Syndrome(Bfls); Mental Retardation PCP0664 Xq25-Xq26 Mental Retardation,X-Linked, With Isolated Growth Hormone Deficiency (Mrgh) Hypertrichosis,Congenital Generalized (Htc2); Mental Retardation, X-Linked, SouthAfrican Type; Borjeson-Forssman-Lehmann Syndrome (Bfls); MentalRetardation With Optic Atrophy, Deafness, And Seizures; MentalRetardation PCP0677 12q15 Scapuloperoneal Myopathy (SPM); Cancers (e.g.,glioma) PCP0762 18q12.1 Cancers PCP0806 2q37.3 Gracile Syndrome;Holoprosencephaly 6 PCP0815 14q11.1-q12 Arrhythmogenic Right VentricularDysplasia, Familial, 3 (Arvd3); Radiation Sensitivity/ChromosomeInstability Syndrome, Autosomal Dominant; Asthma

[0195]

1 39 1 6733 DNA Homo sapiens CDS (575)..(4711) 1 gcgctgccgc tgcggccggctcgaggcacc ggagacagaa tggctgccgg ggcgcccttg 60 accgccgggc gggcgaggcggggctgaccg ccgcctcctt gatcgccccc ttccacgttg 120 ggcgcgccca cttcggggcgcccgctcggc ccccgccctc ctgggcgcgc ggcgctcgga 180 gccgaggcag ttggcgcgggccgcgggcga ggcggggccg cgcgcggggt cccctcctcc 240 tcccggtcag gtcccctcaggagcgccggg cgcagtctgc gcctcccgct ccccgcctcc 300 ggccgggtcc gggacgccgcggctgtgggg tcggcccgct aaggacaagg tcgggagact 360 gggtggcgat gcccgagtgcgactggaggc agccgagcgg aggcgacggc ggttgggatc 420 tgtccctcct gaccggggagcgggactcgg acgggcgccg gtgaggagga ggagaagcgg 480 cggcggagag gttttctgcggccggaattc ccttcaacag catccctgtc ggcgcccgcg 540 agcgcagtct cgccgggcaggggcgccggg gaag atg gag act ggg ggc cgg gcc 595 Met Glu Thr Gly Gly ArgAla 1 5 cgc act ggt acc ccg cag cca gcg gcc ccg ggg gtg tgg agg gct cgg643 Arg Thr Gly Thr Pro Gln Pro Ala Ala Pro Gly Val Trp Arg Ala Arg 1015 20 ccg gcg ggc ggc ggc ggc ggg ggc gcc tcc tcc tgg ctg ctg gac ggg691 Pro Ala Gly Gly Gly Gly Gly Gly Ala Ser Ser Trp Leu Leu Asp Gly 2530 35 aac agc tgg ctg ctg tgc tat ggc ttc ctc tac ctg gcg ctc tac gcg739 Asn Ser Trp Leu Leu Cys Tyr Gly Phe Leu Tyr Leu Ala Leu Tyr Ala 4045 50 55 cag gtg tcc cag tcc aag ccg tgc gag agg acc ggc tcc tgc ttc tcg787 Gln Val Ser Gln Ser Lys Pro Cys Glu Arg Thr Gly Ser Cys Phe Ser 6065 70 ggc cgc tgt gtc aac tcc acc tgc ctc tgc gac ccg ggc tgg gtg ggg835 Gly Arg Cys Val Asn Ser Thr Cys Leu Cys Asp Pro Gly Trp Val Gly 7580 85 gac cag tgc cag cac tgc cag ggc agg ttc aag tta aca gaa cct tct883 Asp Gln Cys Gln His Cys Gln Gly Arg Phe Lys Leu Thr Glu Pro Ser 9095 100 gga tat tta aca gat ggc cca att aac tat aaa tat aaa act aaa tgt931 Gly Tyr Leu Thr Asp Gly Pro Ile Asn Tyr Lys Tyr Lys Thr Lys Cys 105110 115 act tgg ctc att gaa ggc tat cca aat gca gtg tta aga tta aga ttc979 Thr Trp Leu Ile Glu Gly Tyr Pro Asn Ala Val Leu Arg Leu Arg Phe 120125 130 135 aat cat ttt gct aca gaa tgt agc tgg gat cat atg tat gtt tatgat 1027 Asn His Phe Ala Thr Glu Cys Ser Trp Asp His Met Tyr Val Tyr Asp140 145 150 gga gat tca ata tat gca cct tta ata gct gta ctt agt ggt ttgata 1075 Gly Asp Ser Ile Tyr Ala Pro Leu Ile Ala Val Leu Ser Gly Leu Ile155 160 165 gtc cct gaa ata agg ggc aat gaa act gtg cct gaa gtt gtt actaca 1123 Val Pro Glu Ile Arg Gly Asn Glu Thr Val Pro Glu Val Val Thr Thr170 175 180 tct ggc tat gca ctg tta cat ttt ttt agt gat gct gcg tat aatcta 1171 Ser Gly Tyr Ala Leu Leu His Phe Phe Ser Asp Ala Ala Tyr Asn Leu185 190 195 act ggt ttc aac att ttc tat tca atc aat tct tgt cct aac aattgc 1219 Thr Gly Phe Asn Ile Phe Tyr Ser Ile Asn Ser Cys Pro Asn Asn Cys200 205 210 215 tct ggt cat ggg aag tgt aca act agt gtc tct gtt cca agtcaa gta 1267 Ser Gly His Gly Lys Cys Thr Thr Ser Val Ser Val Pro Ser GlnVal 220 225 230 tat tgt gaa tgt gat aaa tac tgg aag ggt gaa gct tgt gatatt cct 1315 Tyr Cys Glu Cys Asp Lys Tyr Trp Lys Gly Glu Ala Cys Asp IlePro 235 240 245 tac tgt aaa gcc aat tgc ggc agt cca gat cac ggt tac tgtgac ctg 1363 Tyr Cys Lys Ala Asn Cys Gly Ser Pro Asp His Gly Tyr Cys AspLeu 250 255 260 act gga gaa aaa tta tgt gtc tgc aat gat agt tgg caa ggtcct gat 1411 Thr Gly Glu Lys Leu Cys Val Cys Asn Asp Ser Trp Gln Gly ProAsp 265 270 275 tgt tct ttg aat gtt ccc tct act gag tct tac tgg att ctgcca aac 1459 Cys Ser Leu Asn Val Pro Ser Thr Glu Ser Tyr Trp Ile Leu ProAsn 280 285 290 295 gtt aaa ccc ttc agt cct tct gta ggt cgg gct tca cataaa gca gtt 1507 Val Lys Pro Phe Ser Pro Ser Val Gly Arg Ala Ser His LysAla Val 300 305 310 tta cac ggg aaa ttt atg tgg gtg att ggt gga tat actttt aac tac 1555 Leu His Gly Lys Phe Met Trp Val Ile Gly Gly Tyr Thr PheAsn Tyr 315 320 325 agt tct ttt caa atg gtc cta aat tac aat tta gaa agcagt ata tgg 1603 Ser Ser Phe Gln Met Val Leu Asn Tyr Asn Leu Glu Ser SerIle Trp 330 335 340 aat gta gga act cca tca agg gga cct ctc cag aga tatgga cac tct 1651 Asn Val Gly Thr Pro Ser Arg Gly Pro Leu Gln Arg Tyr GlyHis Ser 345 350 355 ctt gct tta tat cag gaa aac atc ttt atg tat gga ggcaga att gaa 1699 Leu Ala Leu Tyr Gln Glu Asn Ile Phe Met Tyr Gly Gly ArgIle Glu 360 365 370 375 aca aat gat ggc aat gtc aca gat gaa tta tgg gttttt aac ata cat 1747 Thr Asn Asp Gly Asn Val Thr Asp Glu Leu Trp Val PheAsn Ile His 380 385 390 agt cag tca tgg agt aca aaa act cct act gtt cttgga cat ggt cag 1795 Ser Gln Ser Trp Ser Thr Lys Thr Pro Thr Val Leu GlyHis Gly Gln 395 400 405 cag tat gct gtg gag gga cat tca gca cat att atggag ttg gat agt 1843 Gln Tyr Ala Val Glu Gly His Ser Ala His Ile Met GluLeu Asp Ser 410 415 420 aga gat gtt gtc atg atc ata ata ttt gga tat tctgca ata tat ggt 1891 Arg Asp Val Val Met Ile Ile Ile Phe Gly Tyr Ser AlaIle Tyr Gly 425 430 435 tat aca agc agc ata cag gaa tac cat atc tca tcaaac act tgg ctt 1939 Tyr Thr Ser Ser Ile Gln Glu Tyr His Ile Ser Ser AsnThr Trp Leu 440 445 450 455 gtt cca gaa act aaa gga gct att gta caa ggtgga tat ggc cat act 1987 Val Pro Glu Thr Lys Gly Ala Ile Val Gln Gly GlyTyr Gly His Thr 460 465 470 agt gtg tat gat gaa ata aca aag tcc att tatgtt cat gga ggg tat 2035 Ser Val Tyr Asp Glu Ile Thr Lys Ser Ile Tyr ValHis Gly Gly Tyr 475 480 485 aaa gca ttg cca ggg aac aaa tat gga ttg gttgat gat ctt tat aaa 2083 Lys Ala Leu Pro Gly Asn Lys Tyr Gly Leu Val AspAsp Leu Tyr Lys 490 495 500 tat gaa gtt aac act aag act tgg act att ttgaaa gaa agt ggg ttt 2131 Tyr Glu Val Asn Thr Lys Thr Trp Thr Ile Leu LysGlu Ser Gly Phe 505 510 515 gcc aga tac ctt cat tca gct gtt ctt atc aatgga gct atg ctt att 2179 Ala Arg Tyr Leu His Ser Ala Val Leu Ile Asn GlyAla Met Leu Ile 520 525 530 535 ttt gga gga aat acc cat aat gac act tccttg agt aac ggt gca aaa 2227 Phe Gly Gly Asn Thr His Asn Asp Thr Ser LeuSer Asn Gly Ala Lys 540 545 550 tgt ttt tct gcc gat ttc ctg gca tat gacata gct tgt gat gaa tgg 2275 Cys Phe Ser Ala Asp Phe Leu Ala Tyr Asp IleAla Cys Asp Glu Trp 555 560 565 aaa ata cta cca aaa cca aat ctt cat agagat gtc aac aga ttt gga 2323 Lys Ile Leu Pro Lys Pro Asn Leu His Arg AspVal Asn Arg Phe Gly 570 575 580 cac tct gca gta gtc att aac ggg tcc atgtat ata ttt ggg gga ttt 2371 His Ser Ala Val Val Ile Asn Gly Ser Met TyrIle Phe Gly Gly Phe 585 590 595 tct agt gta ctc ctt aat gat atc ctt gtatac aag cct cca aat tgc 2419 Ser Ser Val Leu Leu Asn Asp Ile Leu Val TyrLys Pro Pro Asn Cys 600 605 610 615 aag gct ttc aga gat gaa gaa ctt tgtaaa aat gct ggt cca ggg ata 2467 Lys Ala Phe Arg Asp Glu Glu Leu Cys LysAsn Ala Gly Pro Gly Ile 620 625 630 aaa tgt gtt tgg aat aaa aat cac tgtgaa tct tgg gaa tct ggg aat 2515 Lys Cys Val Trp Asn Lys Asn His Cys GluSer Trp Glu Ser Gly Asn 635 640 645 act aat aat att ctt aga gca aag tgccct cct aaa aca gct gct tct 2563 Thr Asn Asn Ile Leu Arg Ala Lys Cys ProPro Lys Thr Ala Ala Ser 650 655 660 gat gac aga tgt tac aga tat gca gattgt gcc agc tgt act gcc aat 2611 Asp Asp Arg Cys Tyr Arg Tyr Ala Asp CysAla Ser Cys Thr Ala Asn 665 670 675 aca aat ggg tgc caa tgg tgt gat gacaag aaa tgc att tcg gca aat 2659 Thr Asn Gly Cys Gln Trp Cys Asp Asp LysLys Cys Ile Ser Ala Asn 680 685 690 695 agt aac tgc agt atg tct gtc aagaac tac acc aaa tgt cat gtg aga 2707 Ser Asn Cys Ser Met Ser Val Lys AsnTyr Thr Lys Cys His Val Arg 700 705 710 aat gag cag att tgt aac aaa cttacc agc tgt aaa agc tgt tca cta 2755 Asn Glu Gln Ile Cys Asn Lys Leu ThrSer Cys Lys Ser Cys Ser Leu 715 720 725 aac ttg aat tgc cag tgg gat cagaga cag caa gaa tgc cag gct tta 2803 Asn Leu Asn Cys Gln Trp Asp Gln ArgGln Gln Glu Cys Gln Ala Leu 730 735 740 cca gct cat ctt tgt gga gaa ggatgg agt cat att ggg gat gct tgt 2851 Pro Ala His Leu Cys Gly Glu Gly TrpSer His Ile Gly Asp Ala Cys 745 750 755 ctt aga gtc aat tcc agt aga gaaaac tat gac aat gca aaa ctt tat 2899 Leu Arg Val Asn Ser Ser Arg Glu AsnTyr Asp Asn Ala Lys Leu Tyr 760 765 770 775 tgc tat aat ctt agt gga aatctt gct tca tta aca acc tca aaa gaa 2947 Cys Tyr Asn Leu Ser Gly Asn LeuAla Ser Leu Thr Thr Ser Lys Glu 780 785 790 gta gaa ttt gtt ctg gat gaaata cag aag tat aca caa cag aaa gta 2995 Val Glu Phe Val Leu Asp Glu IleGln Lys Tyr Thr Gln Gln Lys Val 795 800 805 tca cct tgg gta ggc ttg cgcaag atc aat ata tcc tat tgg gga tgg 3043 Ser Pro Trp Val Gly Leu Arg LysIle Asn Ile Ser Tyr Trp Gly Trp 810 815 820 gaa gac atg tct cct ttt acaaac aca aca cta cag tgg ctt cct ggc 3091 Glu Asp Met Ser Pro Phe Thr AsnThr Thr Leu Gln Trp Leu Pro Gly 825 830 835 gaa ccc aat gat tct ggg ttttgt gca tat ctg gaa agg gct gca gtg 3139 Glu Pro Asn Asp Ser Gly Phe CysAla Tyr Leu Glu Arg Ala Ala Val 840 845 850 855 gca ggc tta aaa gct aatcct tgt aca tct atg gca aat ggc ctt gtc 3187 Ala Gly Leu Lys Ala Asn ProCys Thr Ser Met Ala Asn Gly Leu Val 860 865 870 tgt gaa aaa cct gtt gttagt cca aat caa aat gcg agg ccg tgc aaa 3235 Cys Glu Lys Pro Val Val SerPro Asn Gln Asn Ala Arg Pro Cys Lys 875 880 885 aag cca tgc tct ctg aggaca tca tgt tcc aac tgt aca agc aat ggc 3283 Lys Pro Cys Ser Leu Arg ThrSer Cys Ser Asn Cys Thr Ser Asn Gly 890 895 900 atg gag tgt atg tgg tgcagc agt acg aaa cga tgt gtt gac tct aat 3331 Met Glu Cys Met Trp Cys SerSer Thr Lys Arg Cys Val Asp Ser Asn 905 910 915 gcc tat atc atc tct tttcca tat gga caa tgt cta gag tgg caa act 3379 Ala Tyr Ile Ile Ser Phe ProTyr Gly Gln Cys Leu Glu Trp Gln Thr 920 925 930 935 gcc acc tgc tcc cctcta aat tgt tct gga ttg aga acc tgt gga cag 3427 Ala Thr Cys Ser Pro LeuAsn Cys Ser Gly Leu Arg Thr Cys Gly Gln 940 945 950 tgt ttg gaa cag cctgga tgt ggc tgg tgc aat gat cct agt aat aca 3475 Cys Leu Glu Gln Pro GlyCys Gly Trp Cys Asn Asp Pro Ser Asn Thr 955 960 965 gga aga gga cat tgcatt gaa ggt tct tca cgg gga cca atg aag ctt 3523 Gly Arg Gly His Cys IleGlu Gly Ser Ser Arg Gly Pro Met Lys Leu 970 975 980 att gga atg cac cacaat gag atg gtt ctt gac acc aat ctt tgc ccc 3571 Ile Gly Met His His AsnGlu Met Val Leu Asp Thr Asn Leu Cys Pro 985 990 995 aaa gaa aag aac tatgag tgg tcc ttt atc cag tgt cca gct tgc 3616 Lys Glu Lys Asn Tyr Glu TrpSer Phe Ile Gln Cys Pro Ala Cys 1000 1005 1010 cag tgt aat gga cat agcact tgc atc aat aat aat gtg tgc gaa 3661 Gln Cys Asn Gly His Ser Thr CysIle Asn Asn Asn Val Cys Glu 1015 1020 1025 cag tgt aaa aat ctc acc acagga aag cag tgt caa gat tgt atg 3706 Gln Cys Lys Asn Leu Thr Thr Gly LysGln Cys Gln Asp Cys Met 1030 1035 1040 cca ggt tat tat gga gat cca accaat ggt gga cag tgc aca gct 3751 Pro Gly Tyr Tyr Gly Asp Pro Thr Asn GlyGly Gln Cys Thr Ala 1045 1050 1055 tgt aca tgc agt ggc cat gca aat atctgt cat ctg cac aca gga 3796 Cys Thr Cys Ser Gly His Ala Asn Ile Cys HisLeu His Thr Gly 1060 1065 1070 aaa tgt ttc tgc aca act aaa gga ata aaaggt gac caa tgc caa 3841 Lys Cys Phe Cys Thr Thr Lys Gly Ile Lys Gly AspGln Cys Gln 1075 1080 1085 tta tgt gac tct gaa aat cgc tat gtt ggt aatcca ctt aga gga 3886 Leu Cys Asp Ser Glu Asn Arg Tyr Val Gly Asn Pro LeuArg Gly 1090 1095 1100 aca tgt tat tac agc ctt ttg att gat tat caa tttacc ttc agc 3931 Thr Cys Tyr Tyr Ser Leu Leu Ile Asp Tyr Gln Phe Thr PheSer 1105 1110 1115 tta tta cag gaa gat gat cgc cac cat act gcc ata aacttt ata 3976 Leu Leu Gln Glu Asp Asp Arg His His Thr Ala Ile Asn Phe Ile1120 1125 1130 gca aac cca gaa cag tcg aac aaa aat ctg gat ata tca attaat 4021 Ala Asn Pro Glu Gln Ser Asn Lys Asn Leu Asp Ile Ser Ile Asn1135 1140 1145 gca tca aac aac ttt aat ctc aac att tcg tgg tct gtc ggttca 4066 Ala Ser Asn Asn Phe Asn Leu Asn Ile Ser Trp Ser Val Gly Ser1150 1155 1160 aca gct gga aca ata tct ggg gaa gag act tct ata gtt tccaag 4111 Thr Ala Gly Thr Ile Ser Gly Glu Glu Thr Ser Ile Val Ser Lys1165 1170 1175 aat aat ata aag gaa tac aga gat agt ttt tcc tat gaa aaattt 4156 Asn Asn Ile Lys Glu Tyr Arg Asp Ser Phe Ser Tyr Glu Lys Phe1180 1185 1190 aac ttt aga agc aat cct aac att aca ttc tat gtg tac gtcagc 4201 Asn Phe Arg Ser Asn Pro Asn Ile Thr Phe Tyr Val Tyr Val Ser1195 1200 1205 aac ttt tcc tgg cct att aaa ata cag att gca ttc tca caacac 4246 Asn Phe Ser Trp Pro Ile Lys Ile Gln Ile Ala Phe Ser Gln His1210 1215 1220 aat aca atc atg gac ctt gtg cag ttt ttt gtc acc ttc ttcagt 4291 Asn Thr Ile Met Asp Leu Val Gln Phe Phe Val Thr Phe Phe Ser1225 1230 1235 tgt ttc cta tcc tta ttg ctg gtg gct gct gtg gta tgg aagatc 4336 Cys Phe Leu Ser Leu Leu Leu Val Ala Ala Val Val Trp Lys Ile1240 1245 1250 aaa caa act tgt tgg gct tct cga cgg aga gag caa ctg cttcga 4381 Lys Gln Thr Cys Trp Ala Ser Arg Arg Arg Glu Gln Leu Leu Arg1255 1260 1265 gaa cga cag cag atg gcc agc cgt ccc ttt gct tct gtt gatgta 4426 Glu Arg Gln Gln Met Ala Ser Arg Pro Phe Ala Ser Val Asp Val1270 1275 1280 gct ctg gaa gtg gga gct gaa caa aca gag ttt ctg cga gggcca 4471 Ala Leu Glu Val Gly Ala Glu Gln Thr Glu Phe Leu Arg Gly Pro1285 1290 1295 tta gag ggg gca ccc aag cca att gcc att gaa cca tgt gctggg 4516 Leu Glu Gly Ala Pro Lys Pro Ile Ala Ile Glu Pro Cys Ala Gly1300 1305 1310 aac aga gct gct gtt ctg act gtg ttt ctt tgt cta cca cgagga 4561 Asn Arg Ala Ala Val Leu Thr Val Phe Leu Cys Leu Pro Arg Gly1315 1320 1325 tca tca ggt gcc cct ccc cct ggg cag tca ggc ctt gca attgcc 4606 Ser Ser Gly Ala Pro Pro Pro Gly Gln Ser Gly Leu Ala Ile Ala1330 1335 1340 agt gcc cta ata gat att tca caa cag aaa gct tca gat agtaaa 4651 Ser Ala Leu Ile Asp Ile Ser Gln Gln Lys Ala Ser Asp Ser Lys1345 1350 1355 gat aag act tct gga gtc cgg aat cga aaa cac ctt tca acacgt 4696 Asp Lys Thr Ser Gly Val Arg Asn Arg Lys His Leu Ser Thr Arg1360 1365 1370 caa gga act tgt gtc tgagaaatgg aaaccgctcc tgtatattctgtactgtttt 4751 Gln Gly Thr Cys Val 1375 acttcgggct tctgttaaagctgttctatg gccttggatt ttatggaggc agatctctgt 4811 atcatccaga gcctgagtacagtttccttc caaatggaca atgacccagg tggccaaaga 4871 atgttcatga gttttataaaagtattgatg gtcacaggtg ataaagtcag tttttaccac 4931 tatcttaggc ttattatagctaacattaaa ttactctgga aaaagatgta tattgtttct 4991 taatgaagat gaaaaatatgtaattcatat aaatcaactg tttatatccc aagacttgaa 5051 agaaagacat tttttaatgcctgaatgatg agaattgtac agtttttgcc tcataagcaa 5111 acttgaatca cctgtgtatgaacagggaat gaacacattg caatggcttt aaatgctctt 5171 ttatctcgtt gtaaaggtaaggcaagattt tgatgtagta ggatgtaggt aatgtattta 5231 aatatttcat atgaccatatcgtgtccaaa ctcagtctga gaatgtgaca gctttccgcc 5291 taactagaat gcagaccagaatgagttcaa ctcattctgt gcaacttcac agggggttta 5351 ttagaatgct cagtgtagaggacattcctg tcatccatgc caactaccta actcgttatc 5411 agagctgata gagcatggaaaagtctgtcc agcgatcagt tgttcccctc cttccaaaaa 5471 cagcctccaa taccacaacctgaaaagagc cgaaatggtt attttacagc atacaagctt 5531 ctgctccagt atgataatttttaattgcct aagaatcact ggatcagacc taaatgatcc 5591 atctgcattt ttataagaatggatctttct ttgcccttcc tctcctagct gctagatttt 5651 aactaccttt tacaaatgttacaaaatgta ttttagaggc gacatctctc aagatgacct 5711 gagttccttc ctgccaactgttccacctag aatacaagta gagaagagca ctggctggca 5771 agcatcaaca ggagtcttcttcccaacacg agcgcatcca tgtcctgaga aaaagtctgt 5831 ggtttagaaa atatgtccatggttgcccac agtcagcaca ctcttagtga ctcaaaattc 5891 tgaattatgg cagaaaggaaaaataaaaca tacttcacat tagaacacag aatcatttac 5951 atcctaatac tgaccacagttcactaaagc tcagtagcat taacagatat agtttggaat 6011 tgcagtttcc tcacttcagggtgacaagat atgtataaca gtgacagaaa tctccaaagc 6071 tgctgtatat gatatagctttgttaaatat gaaggtcctt taaatacaat tgatgtttag 6131 tactatatat gtacttttcacattctttgg atttctggaa ggttatgaca ctttactgtt 6191 tacagctaat gcatagttacttgcatgcca tggttgtaca gtagcagact atgaccctat 6251 tgtgatatta agtgtttatttcataatgcc atttatacat agctgaattt gatgaggatt 6311 gaatgtcata tataagaggaatgatcatac aatatgtagt tgcatcttat ataagatttc 6371 taggttgcat ctaaccatgactatgtcatt attttgataa ttaggcattt atgaattata 6431 gtatatattc ctcatgttggcatgataatt ttgctatttt ccatgcatta aaaataagac 6491 aaattcttag agtaattttagtaattttat ctataatctg tggggttttt ttggaggggg 6551 aggccactgg ttgtttctacttccctgtga tattttctct ctcattaaag gaatgagcta 6611 agtttgtaaa tatctcctaaaaacaatcaa gtaattttat tagcttcttt tggaccctct 6671 aaatattgac ttctctcatgaaaaaataaa ttgatgaaac taaaaaaaaa aaaaaaaaaa 6731 aa 6733 2 1379 PRT Homosapiens 2 Met Glu Thr Gly Gly Arg Ala Arg Thr Gly Thr Pro Gln Pro AlaAla 1 5 10 15 Pro Gly Val Trp Arg Ala Arg Pro Ala Gly Gly Gly Gly GlyGly Ala 20 25 30 Ser Ser Trp Leu Leu Asp Gly Asn Ser Trp Leu Leu Cys TyrGly Phe 35 40 45 Leu Tyr Leu Ala Leu Tyr Ala Gln Val Ser Gln Ser Lys ProCys Glu 50 55 60 Arg Thr Gly Ser Cys Phe Ser Gly Arg Cys Val Asn Ser ThrCys Leu 65 70 75 80 Cys Asp Pro Gly Trp Val Gly Asp Gln Cys Gln His CysGln Gly Arg 85 90 95 Phe Lys Leu Thr Glu Pro Ser Gly Tyr Leu Thr Asp GlyPro Ile Asn 100 105 110 Tyr Lys Tyr Lys Thr Lys Cys Thr Trp Leu Ile GluGly Tyr Pro Asn 115 120 125 Ala Val Leu Arg Leu Arg Phe Asn His Phe AlaThr Glu Cys Ser Trp 130 135 140 Asp His Met Tyr Val Tyr Asp Gly Asp SerIle Tyr Ala Pro Leu Ile 145 150 155 160 Ala Val Leu Ser Gly Leu Ile ValPro Glu Ile Arg Gly Asn Glu Thr 165 170 175 Val Pro Glu Val Val Thr ThrSer Gly Tyr Ala Leu Leu His Phe Phe 180 185 190 Ser Asp Ala Ala Tyr AsnLeu Thr Gly Phe Asn Ile Phe Tyr Ser Ile 195 200 205 Asn Ser Cys Pro AsnAsn Cys Ser Gly His Gly Lys Cys Thr Thr Ser 210 215 220 Val Ser Val ProSer Gln Val Tyr Cys Glu Cys Asp Lys Tyr Trp Lys 225 230 235 240 Gly GluAla Cys Asp Ile Pro Tyr Cys Lys Ala Asn Cys Gly Ser Pro 245 250 255 AspHis Gly Tyr Cys Asp Leu Thr Gly Glu Lys Leu Cys Val Cys Asn 260 265 270Asp Ser Trp Gln Gly Pro Asp Cys Ser Leu Asn Val Pro Ser Thr Glu 275 280285 Ser Tyr Trp Ile Leu Pro Asn Val Lys Pro Phe Ser Pro Ser Val Gly 290295 300 Arg Ala Ser His Lys Ala Val Leu His Gly Lys Phe Met Trp Val Ile305 310 315 320 Gly Gly Tyr Thr Phe Asn Tyr Ser Ser Phe Gln Met Val LeuAsn Tyr 325 330 335 Asn Leu Glu Ser Ser Ile Trp Asn Val Gly Thr Pro SerArg Gly Pro 340 345 350 Leu Gln Arg Tyr Gly His Ser Leu Ala Leu Tyr GlnGlu Asn Ile Phe 355 360 365 Met Tyr Gly Gly Arg Ile Glu Thr Asn Asp GlyAsn Val Thr Asp Glu 370 375 380 Leu Trp Val Phe Asn Ile His Ser Gln SerTrp Ser Thr Lys Thr Pro 385 390 395 400 Thr Val Leu Gly His Gly Gln GlnTyr Ala Val Glu Gly His Ser Ala 405 410 415 His Ile Met Glu Leu Asp SerArg Asp Val Val Met Ile Ile Ile Phe 420 425 430 Gly Tyr Ser Ala Ile TyrGly Tyr Thr Ser Ser Ile Gln Glu Tyr His 435 440 445 Ile Ser Ser Asn ThrTrp Leu Val Pro Glu Thr Lys Gly Ala Ile Val 450 455 460 Gln Gly Gly TyrGly His Thr Ser Val Tyr Asp Glu Ile Thr Lys Ser 465 470 475 480 Ile TyrVal His Gly Gly Tyr Lys Ala Leu Pro Gly Asn Lys Tyr Gly 485 490 495 LeuVal Asp Asp Leu Tyr Lys Tyr Glu Val Asn Thr Lys Thr Trp Thr 500 505 510Ile Leu Lys Glu Ser Gly Phe Ala Arg Tyr Leu His Ser Ala Val Leu 515 520525 Ile Asn Gly Ala Met Leu Ile Phe Gly Gly Asn Thr His Asn Asp Thr 530535 540 Ser Leu Ser Asn Gly Ala Lys Cys Phe Ser Ala Asp Phe Leu Ala Tyr545 550 555 560 Asp Ile Ala Cys Asp Glu Trp Lys Ile Leu Pro Lys Pro AsnLeu His 565 570 575 Arg Asp Val Asn Arg Phe Gly His Ser Ala Val Val IleAsn Gly Ser 580 585 590 Met Tyr Ile Phe Gly Gly Phe Ser Ser Val Leu LeuAsn Asp Ile Leu 595 600 605 Val Tyr Lys Pro Pro Asn Cys Lys Ala Phe ArgAsp Glu Glu Leu Cys 610 615 620 Lys Asn Ala Gly Pro Gly Ile Lys Cys ValTrp Asn Lys Asn His Cys 625 630 635 640 Glu Ser Trp Glu Ser Gly Asn ThrAsn Asn Ile Leu Arg Ala Lys Cys 645 650 655 Pro Pro Lys Thr Ala Ala SerAsp Asp Arg Cys Tyr Arg Tyr Ala Asp 660 665 670 Cys Ala Ser Cys Thr AlaAsn Thr Asn Gly Cys Gln Trp Cys Asp Asp 675 680 685 Lys Lys Cys Ile SerAla Asn Ser Asn Cys Ser Met Ser Val Lys Asn 690 695 700 Tyr Thr Lys CysHis Val Arg Asn Glu Gln Ile Cys Asn Lys Leu Thr 705 710 715 720 Ser CysLys Ser Cys Ser Leu Asn Leu Asn Cys Gln Trp Asp Gln Arg 725 730 735 GlnGln Glu Cys Gln Ala Leu Pro Ala His Leu Cys Gly Glu Gly Trp 740 745 750Ser His Ile Gly Asp Ala Cys Leu Arg Val Asn Ser Ser Arg Glu Asn 755 760765 Tyr Asp Asn Ala Lys Leu Tyr Cys Tyr Asn Leu Ser Gly Asn Leu Ala 770775 780 Ser Leu Thr Thr Ser Lys Glu Val Glu Phe Val Leu Asp Glu Ile Gln785 790 795 800 Lys Tyr Thr Gln Gln Lys Val Ser Pro Trp Val Gly Leu ArgLys Ile 805 810 815 Asn Ile Ser Tyr Trp Gly Trp Glu Asp Met Ser Pro PheThr Asn Thr 820 825 830 Thr Leu Gln Trp Leu Pro Gly Glu Pro Asn Asp SerGly Phe Cys Ala 835 840 845 Tyr Leu Glu Arg Ala Ala Val Ala Gly Leu LysAla Asn Pro Cys Thr 850 855 860 Ser Met Ala Asn Gly Leu Val Cys Glu LysPro Val Val Ser Pro Asn 865 870 875 880 Gln Asn Ala Arg Pro Cys Lys LysPro Cys Ser Leu Arg Thr Ser Cys 885 890 895 Ser Asn Cys Thr Ser Asn GlyMet Glu Cys Met Trp Cys Ser Ser Thr 900 905 910 Lys Arg Cys Val Asp SerAsn Ala Tyr Ile Ile Ser Phe Pro Tyr Gly 915 920 925 Gln Cys Leu Glu TrpGln Thr Ala Thr Cys Ser Pro Leu Asn Cys Ser 930 935 940 Gly Leu Arg ThrCys Gly Gln Cys Leu Glu Gln Pro Gly Cys Gly Trp 945 950 955 960 Cys AsnAsp Pro Ser Asn Thr Gly Arg Gly His Cys Ile Glu Gly Ser 965 970 975 SerArg Gly Pro Met Lys Leu Ile Gly Met His His Asn Glu Met Val 980 985 990Leu Asp Thr Asn Leu Cys Pro Lys Glu Lys Asn Tyr Glu Trp Ser Phe 995 10001005 Ile Gln Cys Pro Ala Cys Gln Cys Asn Gly His Ser Thr Cys Ile 10101015 1020 Asn Asn Asn Val Cys Glu Gln Cys Lys Asn Leu Thr Thr Gly Lys1025 1030 1035 Gln Cys Gln Asp Cys Met Pro Gly Tyr Tyr Gly Asp Pro ThrAsn 1040 1045 1050 Gly Gly Gln Cys Thr Ala Cys Thr Cys Ser Gly His AlaAsn Ile 1055 1060 1065 Cys His Leu His Thr Gly Lys Cys Phe Cys Thr ThrLys Gly Ile 1070 1075 1080 Lys Gly Asp Gln Cys Gln Leu Cys Asp Ser GluAsn Arg Tyr Val 1085 1090 1095 Gly Asn Pro Leu Arg Gly Thr Cys Tyr TyrSer Leu Leu Ile Asp 1100 1105 1110 Tyr Gln Phe Thr Phe Ser Leu Leu GlnGlu Asp Asp Arg His His 1115 1120 1125 Thr Ala Ile Asn Phe Ile Ala AsnPro Glu Gln Ser Asn Lys Asn 1130 1135 1140 Leu Asp Ile Ser Ile Asn AlaSer Asn Asn Phe Asn Leu Asn Ile 1145 1150 1155 Ser Trp Ser Val Gly SerThr Ala Gly Thr Ile Ser Gly Glu Glu 1160 1165 1170 Thr Ser Ile Val SerLys Asn Asn Ile Lys Glu Tyr Arg Asp Ser 1175 1180 1185 Phe Ser Tyr GluLys Phe Asn Phe Arg Ser Asn Pro Asn Ile Thr 1190 1195 1200 Phe Tyr ValTyr Val Ser Asn Phe Ser Trp Pro Ile Lys Ile Gln 1205 1210 1215 Ile AlaPhe Ser Gln His Asn Thr Ile Met Asp Leu Val Gln Phe 1220 1225 1230 PheVal Thr Phe Phe Ser Cys Phe Leu Ser Leu Leu Leu Val Ala 1235 1240 1245Ala Val Val Trp Lys Ile Lys Gln Thr Cys Trp Ala Ser Arg Arg 1250 12551260 Arg Glu Gln Leu Leu Arg Glu Arg Gln Gln Met Ala Ser Arg Pro 12651270 1275 Phe Ala Ser Val Asp Val Ala Leu Glu Val Gly Ala Glu Gln Thr1280 1285 1290 Glu Phe Leu Arg Gly Pro Leu Glu Gly Ala Pro Lys Pro IleAla 1295 1300 1305 Ile Glu Pro Cys Ala Gly Asn Arg Ala Ala Val Leu ThrVal Phe 1310 1315 1320 Leu Cys Leu Pro Arg Gly Ser Ser Gly Ala Pro ProPro Gly Gln 1325 1330 1335 Ser Gly Leu Ala Ile Ala Ser Ala Leu Ile AspIle Ser Gln Gln 1340 1345 1350 Lys Ala Ser Asp Ser Lys Asp Lys Thr SerGly Val Arg Asn Arg 1355 1360 1365 Lys His Leu Ser Thr Arg Gln Gly ThrCys Val 1370 1375 3 17589 DNA Homo sapiens 3 tctgtgccgg gccctgcgatttgcagcctc caatccatgt ggcaacattc agcgctcact 60 ctatgagggt ttttgtttgggtttcttaac acagcttgac agggcatcac acccaatagt 120 tcagaagctc atctgtcaacacattgtccc tggcaatgtc aagagtctgc tgaagcagcc 180 tattccagag ccaaaaggaggtcggcttat ccaggttgaa ggctactgga ttgcggtggg 240 agacaaggag cctacaatagatgagacgta cattctgaca tcttctgtga agctgaacct 300 gagagatata gtccgagttgtctctgcagg aacctatcca gtgctgattc agggagagac 360 atcagttggt aaaacaagcctgatccagtg gctggctgca gctactggca accactgtgt 420 gcgtattaat aatcacgaacacacggatat tcaggagtac attggttgtt acacgtctga 480 ctcctcaggg aagcttgtctttaaggaagg tagggttaag attccattcc atggacatag 540 gtgtttattc tttcacacacatttccttaa gtaatattct tcatcctttc caattgaggc 600 acatggacct ttgctgtaacagccggcttt tcttgatgcc tgagctaaga tagttaaggg 660 gtgatgcata aggtgctggctttctttagg ttctgctaat cttgctggct gtatacagga 720 ctagggccaa ttttcaagaggggaattgaa ctgctgcttt attttctagg aattcagaga 780 atggggttag tgttagccaaaaggaagttg ggaatagtca acagaatgtg gtgatttaaa 840 tgaaattaga ctgcaggggaaagattacac aagaaatatg aggtattttc agccttggct 900 tcttttctgt ggggaaaaaagggactattt taattgaaaa ttgttcctcc ttgatctgca 960 gtgtcataat ttgttttgaggcaagactag ctacagaaag taatttgctt tgaaatttga 1020 tgataaccta ggatttgttgatttgtacat aatgcatttt aaaactttgt actgatttat 1080 acactagttc ttgctgtttgtttcttccta ggtgttctta ttgatgccat gagaaaaggc 1140 tattggatta ttttagatgaattaaatttg gcccctactg atgtgttaga ggcgctgaat 1200 aggctgttgg atgataaccgtgaattgcta gtaacagaaa cacaggaagt tgttaaagca 1260 caccctcggt ttatgctttttgccacccaa aatcccccag gactttatgg aggcagaaag 1320 gtcctttcta gagccttcaggaatcggttt gtggaattgc actttgatga gttacctagc 1380 tccgagttgg aaacaatcttgcacaagcgg tgtagtttgc caccctccta ttgcagcaag 1440 ttggttaaag tcatgctggatcttcagtcc tatcgcagaa gttcttcagt gtttgctgga 1500 aagcagggct tcatcacccttcgtgatctg ttccgatggg ctgaaagata cagattggct 1560 gagccgaccg agaaggagtatgactggcta cagcatttag ccaatgatgg ttatatgctt 1620 ctggcaggtc gagtcaggaagcaggaggaa attgatgtga ttcaagaagt ccttgagaaa 1680 catttcaaga aaaaattgtgtcctcaatct cttttctcca aagaaaatgt tctaaaattg 1740 ctgggtaaat tgtctactcagatatccaca ttggagtgta actttggcca catcgtgtgg 1800 actgagggca tgcggagactcgcgatgcta gtgggaaggg cattggaatt tggtgaacct 1860 gtgctgctgg ttggagacactgggtgtggg aaaactacta tctgtcaggt atttgcagcc 1920 ttggcaaatc agaaattatactctgtcagc tgccacttac acatggagac atcagacttc 1980 ctgggtggcc tgcggccagtgagacaaaag ccaaacgaca aggaagaaat tgacacatca 2040 agactctttg agtggcatgatgggcctctg gttcaggcca tgaaggagga cggctttttc 2100 ctcttggatg agatctcattggccgatgac tctgtcttgg aaagactcaa cagtgtcctt 2160 gaagtagaaa agtctctggtattagctgaa aaaggcagtc cagaggacaa ggatagtgaa 2220 atagagctgt tgactgctgggaaaaaattt cgtattctag caaccatgaa ccctgggggt 2280 gactttggaa aaaaggagctgtctcctgcc ttaagaaacc ggtttacaga aatatggtgc 2340 cctcaaagca caagccgtgaagatttaatt cagatcatca atcataatct tcgtccagga 2400 ttgtgtctgg gcagaatagatcctaaaggg tctgacatac ctgaagtgat gctggatttc 2460 attgactggc tgacccaccaagagtttggc agaaagtgtg tggtcagtat cagagatatc 2520 ctgtcctggg ttaacttcatgaacaaaatg ggggaggaag ctgctttgaa aaggccagag 2580 atcatctcca ctgtgacatcttttgtccat gctgcatgcc tggtgtacat agatggaata 2640 ggttcagggg taacttcctctgggtttggt acagcccttt tggcacgaaa agaatgtctg 2700 aaatttctaa tcaagaggcttgccaagata gtacgactta cagaatatca gaaaaatgag 2760 ttgaagattt atgacagaatgaaggccaaa gaattcactg gaatagataa cctttgggga 2820 attcatccat tttttataccaaggggtaag aatgattttt aaaaaatgaa ttttcctttt 2880 ctatagatca tagatacttggcttttattg tgacttagtt ttaatgtgta atactcatga 2940 ttatatttgc actaactgagttagattctg acttgagaat aaccataatt gtgtgaatgg 3000 ttgaaaatac ctgactggcatgtaaaaata gagggaaata gagacttcaa tctataaata 3060 gattgtctta tacagtgcttatttttttat tagttggttc ccacattagg aactttccta 3120 tagtaaagct ctaaactctactaatgttga caataaactt ttaagtggct tgcaaagacc 3180 tatttagcct ataatgtatcttaactatac aacctcatca tcttttacag aaacaggttt 3240 tgtgaaccct tgaaggctggtaatgtgtca ttcctgatcc ggtccctggc atctgacatt 3300 taggcctcac agtcataggcactcagaaaa tttctgatgg atgagtgaat gattaaatgg 3360 gaaatgcagt agtctaggagatagtgggtt tgtgttctaa ttctttctct ctttctatct 3420 aactagattg tctctaccaagtatttaaat gaggcagtta gattagctac ttctaaggtg 3480 cttctacttt ttcaggatgttgtttctgta gcagagtcat ctgtttcttg tccctccgcc 3540 ctctctatgt taatgattgatgaatgcctg aagtatatgg agttgcagtg gcaattactg 3600 gggtttcagt ggtgaacataaccagtccag gttccattgc ccttgcccct gtcctcagag 3660 ctccatctct ccttagcagtattctctctt catccctgat gggctgtata atctaaccat 3720 caaatccctt ctctaagccaccatcatagg actcagtgct cctgtgtagg agatacatgc 3780 tagtggccta gaactggggtggtccttgct tctgctacca agggtgaggt aataaatgtt 3840 ttcctagcct cactcccttcaaactggtgt acaaaaaaaa aaaaaaaaaa aaaacgaaaa 3900 caaaacaaaa acttcttccaagagacagtg gcacaaatgt taaatattac aagactgtta 3960 ttagtcctgc atatcagttaacttacaggt taaggacaca gtgtgaattg ttttggtggc 4020 caaaaacatt ggatgaagttgattatgtgg aaccatgtgg cccatatgcc tagcttacac 4080 ttggttttta ggaaagtaactatgaaggta aattgtacaa gtacatacag tgattcaggg 4140 tgtaggttgt gaaaggacaggtgtgtgttt gcatgtacat gtatgtgtat aggagatgga 4200 gagatctgtg tagtaggcactgttgaagaa aacgtgttat tggatattcc tttaaagcat 4260 tttatggatc taaaagtggggaaatattga aatagggatt gaacattttc actgcaaatg 4320 gtatttcact aactgataacccatgtggta gatttttaaa atcttgagtt gatgcataca 4380 tgtgatttga tgatgtcccgcttatacatg actttacttt tctccactta aggacctgtc 4440 ctacacagga ataatattgcagactatgca ctcagtgcag ggaccactgc tatgaatgca 4500 cagaggctct taagagctaccaaactgaag aagcccattc tcctggaggg ttcccctggt 4560 gttggcaaga caagtttggtgggagcatta gcaaaggctt caggaaatac ccttgttaga 4620 atcaacttat cagagcaaacggacatcaca gacctgtttg gagcagatct acctgttgaa 4680 ggtggcaagg gaggagagtttgcctggcgt gatggcccct tactggcagc tttgaaggca 4740 ggccattggg tggtgttggatgagcttaac ctggcttctc agtctgtatt ggaaggactc 4800 aatgcttgtt ttgaccaccgaggagaaatc tatgtgcctg agttaggaat gagctttcaa 4860 gtgcagcatg aaaagacgaagatttttggg tgtcagaatc cctttagaca aggaggtggg 4920 aggaaaggct tgcccaggtctttccttaac agattcactc aggtcttcgt tgatcccctt 4980 acagtaattg acatggagttcattgccagt actttgtttc cagccattga gaaaaatatt 5040 gttaagaaaa tggttgctttcaataaccaa attgatcatg aagtgactgt tgagaagaaa 5100 tgggggcaaa aaggaggaccctgggaattc aacctccggg accttttccg ctggtgtcag 5160 ttgatgctgg ttgaccagtcccctgggtgt tatgatcctg gtcagcatgt gtttttggtc 5220 tatggtgaaa gaatgagaaccgaagaggac aaaaaaaagg tcattgctgt attcaaggat 5280 gtgtttggtt caaattccaacccatacatg ggaaccagac tatttcgtat cactccctat 5340 gatgttcagt tgggctactcagtcctttcc cgtgggagct gtgttcctca cccgtcccgc 5400 catcccctgt tgctcctgcaccagtcattc caacccctgg agtcaatcat gaagtgtgtg 5460 cagatgagct ggatggtcatcctggtcggg ccagcctctg tgggcaagac cagcctggtc 5520 cagcttctgg cacaccttactggccacaca ttaaagatca tggctatgaa cagtgcaatg 5580 gatactactg agctgctgggtggatttgag caggttgatc ttatacgacc ttggaggagg 5640 ctgctagaga aggtggagggaactgtaagg gcactgttaa gggatagcct ccttatcagt 5700 gctgatgatg cagaagtagtgctgcgagcc tggagtcatt ttcttctgac atataagcct 5760 aagtgtcttg gagaaggtggtaaagctatc acgatggaga ttgtcaacaa actagaagca 5820 gtgttattgc ttatgcagcgactcaacaat aaaatcaact catactgcaa ggcagagttt 5880 gccaaacttg ttgaagagttccgaagcttt ggtgtgaagc ttacgcagtt ggccagtggc 5940 catagccatg gcacatttgaatgggttgac agcatgttgg ttcaggccct gaagtctgga 6000 gactggcttc tgatggacaatgttaacttc tgcaacccat cagtgttgga tcgtttgaat 6060 gctttgcttg aacccggaggtgtcctcact attagtgaga gaggaatgat agatggatcc 6120 actcccacga taacaccaaatcccaatttc agacttttcc tctcgatgga tcctgttcat 6180 ggagatatat cccgagctatgaggaatcgt ggacttgaaa tctacatttc aggggaaggg 6240 gatgcaagca ccccagacaacctggatttg aaagttctgc tgcacagcct tggattggtg 6300 gggaacagtg tatgtgacatcctcttggct ttacacacag agacccggag cactgttgta 6360 ggttctccaa catcttctgtatcaactcta atccagacag ccatactaat tgtccagtac 6420 ctgcagcgag ggctgagtttagacagagcc ttttctgaag catgctggga agtatatgtc 6480 tgttcccagc attcaccagcaaaccggaag cttgtacagg ctttactgga gaaacatgtt 6540 tcttctttgc gagcacatgaaacctgggga gactccattc ttggcatggg actgtggcca 6600 gattctgtgc cctcagctctctttgctact gaagattcac acctgtctac agtccgaaga 6660 gatggacaga tcttagtatattgtctcaac aggatgagca tgaaaaccag cagctggaca 6720 aggagtcagc cttttaccttgcaagactta gagaaaatta tgcagtcccc cagccctgag 6780 aacctgaaat tcaatgcagtcgaagtgaat acttactgga tcgatgaacc agatgttttg 6840 gtcatggctg ttaaattgctcatagaaaga gcaaccaatc aggattggat gctcagagtt 6900 aaatggcttt atcatttagccaagaatata ccgcaggggc ttgagtccat acaaattcat 6960 ttggaagcca gtgctgcatctctcaggaat ttttactcac attccctctc aggtgcagtc 7020 agtaatgttt tcaaaatattacaaccaaat acaacagatg aatttgtgat ccctctggat 7080 ccccgatgga atatgcaggctctggacatg attagaaatt tgatggactt tgacccacaa 7140 acagaccagc ctgaccagctctttgccctt ttagaatcag ctgcaaacaa gacaatcata 7200 tatcttgacc gggaaaaacgggtttttact gaagcaaatt tggtttctgt tggtagcaaa 7260 aagctaagag agagtgttttgagaatgtcc tttgaattcc atcaagatcc agaaagctat 7320 cacactctgc cccatgaaattgtggtcaat cttgctgctt tttttgaact ttgtgatgca 7380 ctagtcctgc tctgggtacagtcctcccag ggaatggtgt ctgatgccag tgccaatgag 7440 atcttaggtt ctctgcggtggcgggaccgg ttctggactg tggccgacac agtaaaagta 7500 gatgccccag gtctggcccttcttgccctc cattggcact gggttttaaa acatctggtc 7560 caccagatcc cccgacttctgatgaattat gaagacaaat attacaaaga agttcagact 7620 gtctcagaac atattcagaattgtctgggg agccagactg gtggcttcgc tggtataaag 7680 aagttgcaga agttcctgggacgaccgttt ccttttaagg acaagctggt ggtggagtgt 7740 ttttcacaac tgaaggtccttaacaaagtc cttgccatca gggagcagat gtctgccctt 7800 ggggagagtg gatggcaggaagacattaac cgtctccaag tggttgcttc tcagtggaca 7860 ttaaagaaaa gtctcctgcaagcctgggga ctgatcctca gagcaaatat tttggaagat 7920 gtcagcctag atgaattgaagaattttgtg catgctcagt gtttagaact gaaagccaaa 7980 ggactctcac ttggttttctggagaaaaag catgatgaag cttcctccct gtcccatcca 8040 gacttgacct ccgtaatccacctcaccagg agtgttcagt tgtggcctgc aatggagtac 8100 ctggctatgc tttggcggtacaaagtgaca gctgatttta tggcacaagc ttgtctcaga 8160 agatgcagca aaaatcaacaaccccagata aatgaggaga taagtcacct catctcattt 8220 tgtctttatc acacacctgttacacctcaa gagcttcgag atctgtggtc cttgctgcat 8280 catcagaagg tgtctcctgaagaaattaca tctttgtggt ccgagttatt taattccatg 8340 tttatgtctt tctggagcagtactgtgacc acaaatccag agtactggct aatgtggaac 8400 cctttgcctg gtatgcagcagagggaggca cccaagtctg ttttggactc cacattgaag 8460 ggccccggca atctcaatagacccatattc tctaagtgct gctttgaagt cttaaccagc 8520 agctggagag caagtccctgggatgtgagt ggcctcccca ttctttcctc ctctcacgtg 8580 accctaggag agtgggttgagagaactcag cagctccagg acatcagttc gatgctttgg 8640 actaacatgg ctatctcttcagtagcagaa ttcagacgca cggattccca actccagggg 8700 caggtgctgt tccggcacctggcaggccta gcagagctgc tcccagagtc ccggcggcag 8760 gagtacatgc agaactgtgagcagctgctg cttgggagca gccaggcctt ccagcatgtg 8820 ggccagacac ttggggacatggctggtcag gaggtgctgc ccaaggaact gctctgccag 8880 ttgctcacct ccctgcaccactttgttggt gaaggggaga gtaagaggag cctgcctgag 8940 ccagcccagc gtgggagcctctgggtgagc ctcggcttgc tccagattca gacatggctt 9000 ccccaggcac gctttgaccctgcggtgaag agggagtaca agctcaatta cgtcaaggaa 9060 gagttacacc aactgcagtgtgaatggaag acccggaacc tgtcatccca gctgcagact 9120 ggaagagacc tggaagatgaagtcgttgtc agctactctc atcctcacgt caggctgctt 9180 cgccaaagga tggatcggctggataattta acctgtcacc tgttgaagaa acaggccttt 9240 agaccccagc tgcctgcctacgagtccctg gttcaggaga tccaccacta cgtcaccagc 9300 atcgccaagg cccctgctgttcaggatctg ctcacacggc ttctgcaggc cctccacata 9360 gatgggccac ggtctgcccaagtagcccag agccttctaa aggaggaggc ctcttggcag 9420 cagtcacacc accagttccggaagcggctg tcagaggagt acaccttcta tccagatgcc 9480 gtgagcccac tgcaggcatccatattgcag ttacaacatg gcatgaggct ggtggcctct 9540 gagctccaca cctcactctacagcagtatg gttggtgcag acaggctggg gaccctggcc 9600 acagccttgc tggctttcccatcggtgggc cccaccttcc cgacttacta tgctcatgca 9660 gacactttgt gctcggtgaagtctgaggag gttctacgag gccttgggaa gctaatcctc 9720 aagcgctcag gaggaaaggagctggaaggc aagggccaga aagcctgtcc cactcgggag 9780 cagctgctga tgaatgctctcctttacctg cgctcccacg tgttatgcaa gggagagttg 9840 gaccagaggg ccctgcagctcttcagacat gtgtgtcagg aaatcatcag tgagtgggat 9900 gagcaggaac gcatagcccaagagaaggct gagcaggaaa gcggcctgta tagatacagg 9960 agcaggaact ctaggacagccctgagtgaa gaggaggagg aagaacggga gttcagaaaa 10020 cagttccccc tgcatgaaaaggactttgca gatattttgg tgcagccaac gttggaggag 10080 aacaaaggaa cttcagatgggcaagaagag gaagcaggca caaacccagc tctcctctcc 10140 cagaattcaa tgcaggcagtaatgctgata caccagcaat tgtgtctcaa ctttgctcga 10200 tccctctggt atcaacagactctgccgcca catgaagcaa agcattacct cagcctgttt 10260 ctgtcttgct atcagactggggcatcgctt gtgacacact tctaccccct gatgggagtt 10320 gaactgaatg accgactcttgggcagccaa cttttggcct gtaccctctc ccataacact 10380 ctttttgggg aggcaccctcagacctgatg gtgaaacctg atgggcccta tgacttctac 10440 cagcatccca atgttccagaagcacggcag tgtcaacctg tgcttcaagg tttctcagag 10500 gctgtcagtc acttgctacaggactggcca gaacacccag cgcttgaaca gctcctggtt 10560 gtaatggaca gaattcgtagtttcccactt tccagtccca tctcaaagtt cctgaatggc 10620 ttagagatcc ttctggcaaaggcacaggat tgggaggaaa atgcaagtcg agctttgtct 10680 ttgcggaaac atcttgatttgatcagtcag atgatcattc ggtggcgtaa actggagctg 10740 aactgctggt ccatgagtttggataatact atgaagcgcc acaccgagaa atccaccaag 10800 cactggttct ccatctatcagatgcttgag aagcacatgc aggaacaaac agaagaacag 10860 gaagatgaca aacagatgaccttgatgttg ctggtcagca cattacaagc atttattgaa 10920 ggatcctcgc tgggagagttccatgtgcga cttcagatgt tactggtttt ccattgtcat 10980 gtcttgctga tgccacaggttgaaggaaag gattcacttt gcagtgttct atggaatttg 11040 taccattatt acaagcaattctttgaccgg gtccaggcca aaattgtgga acttcgttcc 11100 cccctagaaa aagaacttaaagaatttgtt aagatttcca agtggaatga tgtcagcttc 11160 tggtccatta agcaatctgtagaaaagaca cacaggacac tctttaaatt catgaagaaa 11220 tttgaagcag tcctgagtgaaccctgccgg tcatccctgg tggagagtga caaggaagaa 11280 cagcctgact ttttgcccaggccaacagat ggagctgcaa gtgaactgtc ttccattcag 11340 aatctgaaca gggcactgagggagaccctg ttagcccaac cagcagctgg gcaggccaca 11400 attccagagt ggtgtcagggcgctgctcct tccggcttgg aaggggagct tctgcgtcgc 11460 ttgccaaagc tcaggaaacgcatgaggaag atgtgcctga cgttcatgaa ggagagcccc 11520 ctgcctcgcc ttgtggagggccttgatcag ttcacaggtg aagtgatttc ctctgtgagt 11580 gagctgcaga gcttaaaggtggaaccctct gcagagaagg agaagcagcg gtcagaagcc 11640 aagcacattc tcatgcaaaaacagcgagct ttgtcagacc tctttaaaca ccttgcaaaa 11700 attggtttgt cgtatcgcaaaggtcttgct tgggcccgtt caaaaaaccc tcaagagatg 11760 cttcatcttc acccattagatctccagagc gcattgtcca tcgtcagcag cactcaggag 11820 gctgattcta ggctgcttacagaaatctcg tcttcatggg atggatgcca gaagtatttt 11880 tatcgctctc ttgcacggcatgccaggctt aacgcagcac tagcaactcc tgccaaggaa 11940 atgggcatgg gcaacgtggagaggtgcaga gggttctcag cacatttgat gaagatgctc 12000 gtccgacagc ggcgctccctgaccacgctc agtgagcagt ggatcatcct caggaacctc 12060 ctcagctgtg tgcaagagattcacagcagg ctgatggggc cccaggccta ccccgtggcc 12120 ttcccccctc aggatggcgtgcagcagtgg acagagcgcc tgcagcacct ggccatgcag 12180 tgccagatcc tgcttgagcagctctcctgg ctcctccagt gctgccccag tgtagggcca 12240 gctccaggcc atggcaatgtccaggtactg gggcagcctc ctggcccctg cctggaagga 12300 ccagaactta gcaagggacaactttgtgga gtagtgctgg acctaattcc ttccaatctg 12360 agctacccat ctccaatacctggaagtcag ctgccctctg gttgccggat gcggaaacag 12420 gatcaccttt ggcaacagtcaactacgaga ttaacagaga tgctaaaaac cattaaaaca 12480 gtgaaagctg acgtcgacaaaattagacag cagtcttgtg agactctctt tcattcttgg 12540 aaagattttg aagtttgctcttctgcgctg agttgcttgt cccaggtgtc agttcatttg 12600 cagggcctag agtccttgttcattcttcca gggatggagg ttgagcaaag agactcacaa 12660 atggcactag ttgaaagtctggaatatgta agaggagaaa ttagtaaagc catggctgac 12720 tttactacct ggaagacccatctgcttact tcagatagcc aaggaggaaa tcaaatgttg 12780 gacgaaggat ttgtggaagatttttcagag caaatggaaa ttgccatccg agccatcctc 12840 tgtgccatcc agaacttagaagaaagaaag aatgaaaaag cagaggagaa cactgaccaa 12900 gcaagcccac aagaagattatgcaggcttt gagagactgc aatcaggaca tctaacaaaa 12960 ctcttagagg atgacttctgggccgatgtg agcactttgc acgtgcagaa aataatttct 13020 gccatctccg agctgttggagaggctgaaa tcgtacggtg aggatggcac agcagcaaag 13080 cacctgttct tcagccaatcctgttccttg ctggtgcgcc tggtgccggt cctctccagc 13140 tactcagacc tcgtcctcttcttcctgacc atgtctttag caactcaccg tagtactgca 13200 aagctgctct ctgtgcttgcccaggtcttt acagagcttg cccagaaggg attttgcttg 13260 cccaaagaat ttatggaagattcagctgga gagggagcaa ctgagttcca tgactatgag 13320 ggaggtggaa ttggagaaggcgagggcatg aaggatgtga gtgaccagat cggaaatgaa 13380 gaacaggtgg aagatacatttcagaagggt caagaaaaag acaaagagga tcctgattca 13440 aaatctgata ttaagggcgaggataatgcc attgagatgt cggaagattt tgatgggaaa 13500 atgcatgatg gggagcttgaagaacaagaa gaggatgatg agaaatcaga tagtgagggc 13560 ggagacctgg ataaacacatgggcgatctc aatggtgagg aagctgacaa actagatgag 13620 aggctttggg gtgatgatgatgaggaggaa gatgaggagg aagaagacaa taaaactgaa 13680 gaaacaggac caggaatggatgaggaagat tctgaacttg ttgctaaaga tgacaacttg 13740 gatagtggca attcaaacaaagataaaagc cagcaagata agaaggaaga aaaggaagaa 13800 gcagaagctg atgatggtggacaaggtgaa gacaaaatta atgaacaaat agatgagagg 13860 gactatgatg aaaatgaggtggacccttac catggcaatc aggaaaaggt gccagaaccc 13920 gaggctttgg accttccagatgacttgaac ctcgacagtg aagacaagaa tggtggtgag 13980 gacaccgaca atgaagaaggagaagaagag aatcctttgg agataaaaga aaaaccagaa 14040 gaagcaggtc atgaagctgaggaaagagga gagaccgaga ccgaccagaa cgaaagtcag 14100 agtccacagg agcctgaggaaggccccagt gaagatgaca aggcagaagg ggaagaggaa 14160 atggacacag gagctgatgaccaagatgga gatgctgctc agcatcctga agaacactct 14220 gaggagcagc agcagtctgtggaggaaaaa gacaaggaag ccgatgaaga aggtggagag 14280 aatggccctg ctgaccaaggtttccagccc caggaggaag aagaacggga ggactctgat 14340 acagaggagc aggtgccagaggctttggag aggaaggagc atgcctcctg tgggcagact 14400 ggtgtggaga acatgcagaacacacaggcc atggagctgg ctggggccgc acctgagaag 14460 gagcagggga aagaggaacacggaagtgga gctgcagatg caaaccaggc agaaggccat 14520 gaatcgaatt tcattgcccagttggcctcc cagaagcaca ccaggaaaaa cacacagagt 14580 tttaagagga aacctgggcaggctgacaat gaacgttcca tgggtgatca caatgagcgt 14640 gtgcacaaga ggctgaggactgtggatacg gacagccatg ccgagcaggg gccagctcag 14700 cagccccagg cccaggtggaggatgcagat gcattcgagc acattaaaca aggcagtgac 14760 gcatacgatg cacagacctatgatgtggcc agcaaagaac agcaacagtc tgcaaaagac 14820 tctggcaaag atcaggaagaggaggagata gaggacaccc ttatggacac agaggagcag 14880 gaggagttca aagcagcagacgtggagcag ctgaagccag aggaaatcaa gtcgggcacc 14940 acagcaccct tgggctttgatgagatggaa gtggagatcc aaactgttaa aacagaggaa 15000 gaccaagacc ccagaacagacaaagcccat aaggagacag aaaatgagaa accagaaaga 15060 agccgagagt ctaccattcatacagctcat caattcctca tggacacgat cttccagccc 15120 tttttaaaag atgtcaatgagctaagacag gagctggaga gacagctgga aatgtggcag 15180 ccacgtgaat ctggaaacccagaggaggag aaggttgcag ctgagatgtg gcagagttac 15240 ctgatcttaa cagcgcctctttcacaacgg ttatgtgaag agcttcgtct catattagag 15300 cctacccagg cagccaagctgaaaggagac tatcgaactg ggaaacgact aaacatacgg 15360 aaagtcattc catacattgctagtcaattt cggaaagaca agatttggct tcgaaggacc 15420 aagcccagta aacgccagtatcagatttgt ttggctatcg atgactcttc tagtatggta 15480 gacaatcata ccaagcagcttgcatttgaa tctttggctg tgattggaaa tgctctaacc 15540 ctcctggaag tgggtcagattgcagtgtgt agttttggag aatctgtaaa gctgttacac 15600 ccatttcatg agcagttcagtgattactct gggtcccaga ttctacgtct ctgcaaattc 15660 caacaaaaga aaaccaagattgctcagttt ctagagtctg ttgccaacat gtttgcagct 15720 gctcagcagc tctcgcagaacatcagttca gaaactgcac aactcctcct ggtagtctct 15780 gatgggcgag gccttttccttgagggcaaa gaaagagtcc tggcagcagt tcaggctgcc 15840 cggaatgcaa atatctttgtcatctttgtt gtattggaca atcccagttc acgggattct 15900 atcttggaca ttaaagtaccgatatttaaa ggacctggag agatgcctga aatccgatcc 15960 tacatggaag agttcccattcccatactat atcattcttc gagatgtaaa cgcacttcct 16020 gagacactca gcgatgccctcagacagtgg tttgagttgg tgacagcctc tgaccaccca 16080 tagaacagaa agaagagtccaaagtgagac ttaactgtgg tcagaaggtc acattgctta 16140 cccaggtgct cccttttggacaactacaaa aaattttatt gtaatatttt tattttacaa 16200 cgtgatctta cagcctacagaatgctctct ggctcccggc tttgcctggg ctgaggtttt 16260 tataccaaac ctggaagcagcagcaggtgc ctgaactcgt aactagagaa gagttatcct 16320 tcttccctgc cttggaagccctggcctggg aggaggtcat accccaccgt tggagcccag 16380 ctgcctgttt tcttttgcaggggatctggg cacctgtgcc ttgaggagat gctgccagga 16440 gcatgggact ctgacagtcctttgtataaa ggactaaagg gagctgccct tttgaccctg 16500 ttctaagctc tgccttgccaagcccatagt gtgtgcccaa aagctgtcaa gtggccaaga 16560 cagctcgttt ctggagagtatgagggtgtg ttttcttatt gtgaaaggaa ctaccttctc 16620 ttagagggta ggaagaatgtggtgtgtgtg tgttctcata aagcaactgg acattatagg 16680 tgcccaggtc atctataaaaacgatccttg ggctgtgtaa aaatgaagtg gcttttcagt 16740 atcctctttc acacttgctgcttcgggaga ctatgcaatg atgggaaggt gattgcccct 16800 ttatttcatt cagtgccatggtccctgttg ttgtagtaat ttatttgttt agttcatttt 16860 tttttttctt aacagtcaaggggaagagtg attcctcaca ctgctttcaa gctggactga 16920 gccagtctca ttctgggaaagaaacgctgt gtccagaact cagcagctcc atctattttt 16980 tccagtcgaa agaaactgatctttaggcag tttttacttg gccagaaagc agtgctgaat 17040 acttgaaact gtgtgctctgttctacttaa tgttctgtca gaatgttctt ttgtaggcag 17100 tatgtcatga tgtaatcatctatctccttg tctgtttcca agttacactg tgaagtctgc 17160 gacccttttg aggtggtcatcaaagacaca gattccttgt ttaaccaagt gtcccaaagc 17220 atgtacctga agttatatcattttttattc taaaaagcta tgcagcttat attctgaaaa 17280 ctattaaaac atataccactgttgttgatg taatttgtga ctcttcttaa tggaagatga 17340 caggattgta aaaggtatgctaggggactg atcttctctg ctggatcagt cagtcagctg 17400 ttactagttg atgctgtgctaacatgatcc cctcctactt ccatgttgct cttactacaa 17460 aggttatcat ttgcatttatgtccatggta ggctgagcta taatatgctg gctttgcagc 17520 agaatgaaaa ggatgagttggtgtagcctt ataaggaggc ttataaaaat taattatcct 17580 ccataaatg 17589 4 3890DNA Homo sapiens CDS (1129)..(2862) 4 tctgtgccgg gccctgcgat ttgcagcctccaatccatgt ggcaacattc agcgctcact 60 ctatgagggt ttttgtttgg gtttcttaacacagcttgac agggcatcac acccaatagt 120 tcagaagctc atctgtcaac acattgtccctggcaatgtc aagagtctgc tgaagcagcc 180 tattccagag ccaaaaggag gtcggcttatccaggttgaa ggctactgga ttgcggtggg 240 agacaaggag cctacaatag atgagacgtacattctgaca tcttctgtga agctgaacct 300 gagagatata gtccgagttg tctctgcaggaacctatcca gtgctgattc agggagagac 360 atcagttggt aaaacaagcc tgatccagtggctggctgca gctactggca accactgtgt 420 gcgtattaat aatcacgaac acacggatattcaggagtac attggttgtt acacgtctga 480 ctcctcaggg aagcttgtct ttaaggaaggtagggttaag attccattcc atggacatag 540 gtgtttattc tttcacacac atttccttaagtaatattct tcatcctttc caattgaggc 600 acatggacct ttgctgtaac agccggcttttcttgatgcc tgagctaaga tagttaaggg 660 gtgatgcata aggtgctggc tttctttaggttctgctaat cttgctggct gtatacagga 720 ctagggccaa ttttcaagag gggaattgaactgctgcttt attttctagg aattcagaga 780 atggggttag tgttagccaa aaggaagttgggaatagtca acagaatgtg gtgatttaaa 840 tgaaattaga ctgcagggga aagattacacaagaaatatg aggtattttc agccttggct 900 tcttttctgt ggggaaaaaa gggactattttaattgaaaa ttgttcctcc ttgatctgca 960 gtgtcataat ttgttttgag gcaagactagctacagaaag taatttgctt tgaaatttga 1020 tgataaccta ggatttgttg atttgtacataatgcatttt aaaactttgt actgatttat 1080 acactagttc ttgctgtttg tttcttcctaggtgttctta ttgatgcc atg aga aaa 1137 Met Arg Lys 1 ggc tat tgg att atttta gat gaa tta aat ttg gcc cct act gat gtg 1185 Gly Tyr Trp Ile Ile LeuAsp Glu Leu Asn Leu Ala Pro Thr Asp Val 5 10 15 tta gag gcg ctg aat aggctg ttg gat gat aac cgt gaa ttg cta gta 1233 Leu Glu Ala Leu Asn Arg LeuLeu Asp Asp Asn Arg Glu Leu Leu Val 20 25 30 35 aca gaa aca cag gaa gttgtt aaa gca cac cct cgg ttt atg ctt ttt 1281 Thr Glu Thr Gln Glu Val ValLys Ala His Pro Arg Phe Met Leu Phe 40 45 50 gcc acc caa aat ccc cca ggactt tat gga ggc aga aag gtc ctt tct 1329 Ala Thr Gln Asn Pro Pro Gly LeuTyr Gly Gly Arg Lys Val Leu Ser 55 60 65 aga gcc ttc agg aat cgg ttt gtggaa ttg cac ttt gat gag tta cct 1377 Arg Ala Phe Arg Asn Arg Phe Val GluLeu His Phe Asp Glu Leu Pro 70 75 80 agc tcc gag ttg gaa aca atc ttg cacaag cgg tgt agt ttg cca ccc 1425 Ser Ser Glu Leu Glu Thr Ile Leu His LysArg Cys Ser Leu Pro Pro 85 90 95 tcc tat tgc agc aag ttg gtt aaa gtc atgctg gat ctt cag tcc tat 1473 Ser Tyr Cys Ser Lys Leu Val Lys Val Met LeuAsp Leu Gln Ser Tyr 100 105 110 115 cgc aga agt tct tca gtg ttt gct ggaaag cag ggc ttc atc acc ctt 1521 Arg Arg Ser Ser Ser Val Phe Ala Gly LysGln Gly Phe Ile Thr Leu 120 125 130 cgt gat ctg ttc cga tgg gct gaa agatac aga ttg gct gag ccg acc 1569 Arg Asp Leu Phe Arg Trp Ala Glu Arg TyrArg Leu Ala Glu Pro Thr 135 140 145 gag aag gag tat gac tgg cta cag cattta gcc aat gat ggt tat atg 1617 Glu Lys Glu Tyr Asp Trp Leu Gln His LeuAla Asn Asp Gly Tyr Met 150 155 160 ctt ctg gca ggt cga gtc agg aag caggag gaa att gat gtg att caa 1665 Leu Leu Ala Gly Arg Val Arg Lys Gln GluGlu Ile Asp Val Ile Gln 165 170 175 gaa gtc ctt gag aaa cat ttc aag aaaaaa ttg tgt cct caa tct ctt 1713 Glu Val Leu Glu Lys His Phe Lys Lys LysLeu Cys Pro Gln Ser Leu 180 185 190 195 ttc tcc aaa gaa aat gtt cta aaattg ctg ggt aaa ttg tct act cag 1761 Phe Ser Lys Glu Asn Val Leu Lys LeuLeu Gly Lys Leu Ser Thr Gln 200 205 210 ata tcc aca ttg gag tgt aac tttggc cac atc gtg tgg act gag ggc 1809 Ile Ser Thr Leu Glu Cys Asn Phe GlyHis Ile Val Trp Thr Glu Gly 215 220 225 atg cgg aga ctc gcg atg cta gtggga agg gca ttg gaa ttt ggt gaa 1857 Met Arg Arg Leu Ala Met Leu Val GlyArg Ala Leu Glu Phe Gly Glu 230 235 240 cct gtg ctg ctg gtt gga gac actggg tgt ggg aaa act act atc tgt 1905 Pro Val Leu Leu Val Gly Asp Thr GlyCys Gly Lys Thr Thr Ile Cys 245 250 255 cag gta ttt gca gcc ttg gca aatcag aaa tta tac tct gtc agc tgc 1953 Gln Val Phe Ala Ala Leu Ala Asn GlnLys Leu Tyr Ser Val Ser Cys 260 265 270 275 cac tta cac atg gag aca tcagac ttc ctg ggt ggc ctg cgg cca gtg 2001 His Leu His Met Glu Thr Ser AspPhe Leu Gly Gly Leu Arg Pro Val 280 285 290 aga caa aag cca aac gac aaggaa gaa att gac aca tca aga ctc ttt 2049 Arg Gln Lys Pro Asn Asp Lys GluGlu Ile Asp Thr Ser Arg Leu Phe 295 300 305 gag tgg cat gat ggg cct ctggtt cag gcc atg aag gag gac ggc ttt 2097 Glu Trp His Asp Gly Pro Leu ValGln Ala Met Lys Glu Asp Gly Phe 310 315 320 ttc ctc ttg gat gag atc tcattg gcc gat gac tct gtc ttg gaa aga 2145 Phe Leu Leu Asp Glu Ile Ser LeuAla Asp Asp Ser Val Leu Glu Arg 325 330 335 ctc aac agt gtc ctt gaa gtagaa aag tct ctg gta tta gct gaa aaa 2193 Leu Asn Ser Val Leu Glu Val GluLys Ser Leu Val Leu Ala Glu Lys 340 345 350 355 ggc agt cca gag gac aaggat agt gaa ata gag ctg ttg act gct ggg 2241 Gly Ser Pro Glu Asp Lys AspSer Glu Ile Glu Leu Leu Thr Ala Gly 360 365 370 aaa aaa ttt cgt att ctagca acc atg aac cct ggg ggt gac ttt gga 2289 Lys Lys Phe Arg Ile Leu AlaThr Met Asn Pro Gly Gly Asp Phe Gly 375 380 385 aaa aag gag ctg tct cctgcc tta aga aac cgg ttt aca gaa ata tgg 2337 Lys Lys Glu Leu Ser Pro AlaLeu Arg Asn Arg Phe Thr Glu Ile Trp 390 395 400 tgc cct caa agc aca agccgt gaa gat tta att cag atc atc aat cat 2385 Cys Pro Gln Ser Thr Ser ArgGlu Asp Leu Ile Gln Ile Ile Asn His 405 410 415 aat ctt cgt cca gga ttgtgt ctg ggc aga ata gat cct aaa ggg tct 2433 Asn Leu Arg Pro Gly Leu CysLeu Gly Arg Ile Asp Pro Lys Gly Ser 420 425 430 435 gac ata cct gaa gtgatg ctg gat ttc att gac tgg ctg acc cac caa 2481 Asp Ile Pro Glu Val MetLeu Asp Phe Ile Asp Trp Leu Thr His Gln 440 445 450 gag ttt ggc aga aagtgt gtg gtc agt atc aga gat atc ctg tcc tgg 2529 Glu Phe Gly Arg Lys CysVal Val Ser Ile Arg Asp Ile Leu Ser Trp 455 460 465 gtt aac ttc atg aacaaa atg ggg gag gaa gct gct ttg aaa agg cca 2577 Val Asn Phe Met Asn LysMet Gly Glu Glu Ala Ala Leu Lys Arg Pro 470 475 480 gag atc atc tcc actgtg aca tct ttt gtc cat gct gca tgc ctg gtg 2625 Glu Ile Ile Ser Thr ValThr Ser Phe Val His Ala Ala Cys Leu Val 485 490 495 tac ata gat gga ataggt tca ggg gta act tcc tct ggg ttt ggt aca 2673 Tyr Ile Asp Gly Ile GlySer Gly Val Thr Ser Ser Gly Phe Gly Thr 500 505 510 515 gcc ctt ttg gcacga aaa gaa tgt ctg aaa ttt cta atc aag agg ctt 2721 Ala Leu Leu Ala ArgLys Glu Cys Leu Lys Phe Leu Ile Lys Arg Leu 520 525 530 gcc aag ata gtacga ctt aca gaa tat cag aaa aat gag ttg aag att 2769 Ala Lys Ile Val ArgLeu Thr Glu Tyr Gln Lys Asn Glu Leu Lys Ile 535 540 545 tat gac aga atgaag gcc aaa gaa ttc act gga ata gat aac ctt tgg 2817 Tyr Asp Arg Met LysAla Lys Glu Phe Thr Gly Ile Asp Asn Leu Trp 550 555 560 gga att cat ccattt ttt ata cca agg ggt aag aat gat ttt taa 2862 Gly Ile His Pro Phe PheIle Pro Arg Gly Lys Asn Asp Phe 565 570 575 aaaatgaatt ttccttttctatagatcata gatacttggc ttttattgtg acttagtttt 2922 aatgtgtaat actcatgattatatttgcac taactgagtt agattctgac ttgagaataa 2982 ccataattgt gtgaatggttgaaaatacct gactggcatg taaaaataga gggaaataga 3042 gacttcaatc tataaatagattgtcttata cagtgcttat ttttttatta gttggttccc 3102 acattaggaa ctttcctatagtaaagctct aaactctact aatgttgaca ataaactttt 3162 aagtggcttg caaagacctatttagcctat aatgtatctt aactatacaa cctcatcatc 3222 ttttacagaa acaggttttgtgaacccttg aaggctggta atgtgtcatt cctgatccgg 3282 tccctggcat ctgacatttaggcctcacag tcataggcac tcagaaaatt tctgatggat 3342 gagtgaatga ttaaatgggaaatgcagtag tctaggagat agtgggtttg tgttctaatt 3402 ctttctctct ttctatctaactagattgtc tctaccaagt atttaaatga ggcagttaga 3462 ttagctactt ctaaggtgcttctacttttt caggatgttg tttctgtagc agagtcatct 3522 gtttcttgtc cctccgccctctctatgtta atgattgatg aatgcctgaa gtatatggag 3582 ttgcagtggc aattactggggtttcagtgg tgaacataac cagtccaggt tccattgccc 3642 ttgcccctgt cctcagagctccatctctcc ttagcagtat tctctcttca tccctgatgg 3702 gctgtataat ctaaccatcaaatcccttct ctaagccacc atcataggac tcagtgctcc 3762 tgtgtaggag atacatgctagtggcctaga actggggtgg tccttgcttc tgctaccaag 3822 ggtgaggtaa taaatgttttcctagcctca ctcccttcaa actggtgtac aaaaaaaaaa 3882 aaaaaaaa 3890 5 577 PRTHomo sapiens 5 Met Arg Lys Gly Tyr Trp Ile Ile Leu Asp Glu Leu Asn LeuAla Pro 1 5 10 15 Thr Asp Val Leu Glu Ala Leu Asn Arg Leu Leu Asp AspAsn Arg Glu 20 25 30 Leu Leu Val Thr Glu Thr Gln Glu Val Val Lys Ala HisPro Arg Phe 35 40 45 Met Leu Phe Ala Thr Gln Asn Pro Pro Gly Leu Tyr GlyGly Arg Lys 50 55 60 Val Leu Ser Arg Ala Phe Arg Asn Arg Phe Val Glu LeuHis Phe Asp 65 70 75 80 Glu Leu Pro Ser Ser Glu Leu Glu Thr Ile Leu HisLys Arg Cys Ser 85 90 95 Leu Pro Pro Ser Tyr Cys Ser Lys Leu Val Lys ValMet Leu Asp Leu 100 105 110 Gln Ser Tyr Arg Arg Ser Ser Ser Val Phe AlaGly Lys Gln Gly Phe 115 120 125 Ile Thr Leu Arg Asp Leu Phe Arg Trp AlaGlu Arg Tyr Arg Leu Ala 130 135 140 Glu Pro Thr Glu Lys Glu Tyr Asp TrpLeu Gln His Leu Ala Asn Asp 145 150 155 160 Gly Tyr Met Leu Leu Ala GlyArg Val Arg Lys Gln Glu Glu Ile Asp 165 170 175 Val Ile Gln Glu Val LeuGlu Lys His Phe Lys Lys Lys Leu Cys Pro 180 185 190 Gln Ser Leu Phe SerLys Glu Asn Val Leu Lys Leu Leu Gly Lys Leu 195 200 205 Ser Thr Gln IleSer Thr Leu Glu Cys Asn Phe Gly His Ile Val Trp 210 215 220 Thr Glu GlyMet Arg Arg Leu Ala Met Leu Val Gly Arg Ala Leu Glu 225 230 235 240 PheGly Glu Pro Val Leu Leu Val Gly Asp Thr Gly Cys Gly Lys Thr 245 250 255Thr Ile Cys Gln Val Phe Ala Ala Leu Ala Asn Gln Lys Leu Tyr Ser 260 265270 Val Ser Cys His Leu His Met Glu Thr Ser Asp Phe Leu Gly Gly Leu 275280 285 Arg Pro Val Arg Gln Lys Pro Asn Asp Lys Glu Glu Ile Asp Thr Ser290 295 300 Arg Leu Phe Glu Trp His Asp Gly Pro Leu Val Gln Ala Met LysGlu 305 310 315 320 Asp Gly Phe Phe Leu Leu Asp Glu Ile Ser Leu Ala AspAsp Ser Val 325 330 335 Leu Glu Arg Leu Asn Ser Val Leu Glu Val Glu LysSer Leu Val Leu 340 345 350 Ala Glu Lys Gly Ser Pro Glu Asp Lys Asp SerGlu Ile Glu Leu Leu 355 360 365 Thr Ala Gly Lys Lys Phe Arg Ile Leu AlaThr Met Asn Pro Gly Gly 370 375 380 Asp Phe Gly Lys Lys Glu Leu Ser ProAla Leu Arg Asn Arg Phe Thr 385 390 395 400 Glu Ile Trp Cys Pro Gln SerThr Ser Arg Glu Asp Leu Ile Gln Ile 405 410 415 Ile Asn His Asn Leu ArgPro Gly Leu Cys Leu Gly Arg Ile Asp Pro 420 425 430 Lys Gly Ser Asp IlePro Glu Val Met Leu Asp Phe Ile Asp Trp Leu 435 440 445 Thr His Gln GluPhe Gly Arg Lys Cys Val Val Ser Ile Arg Asp Ile 450 455 460 Leu Ser TrpVal Asn Phe Met Asn Lys Met Gly Glu Glu Ala Ala Leu 465 470 475 480 LysArg Pro Glu Ile Ile Ser Thr Val Thr Ser Phe Val His Ala Ala 485 490 495Cys Leu Val Tyr Ile Asp Gly Ile Gly Ser Gly Val Thr Ser Ser Gly 500 505510 Phe Gly Thr Ala Leu Leu Ala Arg Lys Glu Cys Leu Lys Phe Leu Ile 515520 525 Lys Arg Leu Ala Lys Ile Val Arg Leu Thr Glu Tyr Gln Lys Asn Glu530 535 540 Leu Lys Ile Tyr Asp Arg Met Lys Ala Lys Glu Phe Thr Gly IleAsp 545 550 555 560 Asn Leu Trp Gly Ile His Pro Phe Phe Ile Pro Arg GlyLys Asn Asp 565 570 575 Phe 6 14101 DNA Homo sapiens CDS (1039)..(12630)6 gcagttagat tagctacttc taaggtgctt ctactttttc aggatgttgt ttctgtagca 60gagtcatctg tttcttgtcc ctccgccctc tctatgttaa tgattgatga atgcctgaag 120tatatggagt tgcagtggca attactgggg tttcagtggt gaacataacc agtccaggtt 180ccattgccct tgcccctgtc ctcagagctc catctctcct tagcagtatt ctctcttcat 240ccctgatggg ctgtataatc taaccatcaa atcccttctc taagccacca tcataggact 300cagtgctcct gtgtaggaga tacatgctag tggcctagaa ctggggtggt ccttgcttct 360gctaccaagg gtgaggtaat aaatgttttc ctagcctcac tcccttcaaa ctggtgtaca 420aaaaaaaaaa aaaaaaaaaa acgaaaacaa aacaaaaact tcttccaaga gacagtggca 480caaatgttaa atattacaag actgttatta gtcctgcata tcagttaact tacaggttaa 540ggacacagtg tgaattgttt tggtggccaa aaacattgga tgaagttgat tatgtggaac 600catgtggccc atatgcctag cttacacttg gtttttagga aagtaactat gaaggtaaat 660tgtacaagta catacagtga ttcagggtgt aggttgtgaa aggacaggtg tgtgtttgca 720tgtacatgta tgtgtatagg agatggagag atctgtgtag taggcactgt tgaagaaaac 780gtgttattgg atattccttt aaagcatttt atggatctaa aagtggggaa atattgaaat 840agggattgaa cattttcact gcaaatggta tttcactaac tgataaccca tgtggtagat 900ttttaaaatc ttgagttgat gcatacatgt gatttgatga tgtcccgctt atacatgact 960ttacttttct ccacttaagg acctgtccta cacaggaata atattgcaga ctatgcactc 1020agtgcaggga ccactgct atg aat gca cag agg ctc tta aga gct acc aaa 1071 MetAsn Ala Gln Arg Leu Leu Arg Ala Thr Lys 1 5 10 ctg aag aag ccc att ctcctg gag ggt tcc cct ggt gtt ggc aag aca 1119 Leu Lys Lys Pro Ile Leu LeuGlu Gly Ser Pro Gly Val Gly Lys Thr 15 20 25 agt ttg gtg gga gca tta gcaaag gct tca gga aat acc ctt gtt aga 1167 Ser Leu Val Gly Ala Leu Ala LysAla Ser Gly Asn Thr Leu Val Arg 30 35 40 atc aac tta tca gag caa acg gacatc aca gac ctg ttt gga gca gat 1215 Ile Asn Leu Ser Glu Gln Thr Asp IleThr Asp Leu Phe Gly Ala Asp 45 50 55 cta cct gtt gaa ggt ggc aag gga ggagag ttt gcc tgg cgt gat ggc 1263 Leu Pro Val Glu Gly Gly Lys Gly Gly GluPhe Ala Trp Arg Asp Gly 60 65 70 75 ccc tta ctg gca gct ttg aag gca ggccat tgg gtg gtg ttg gat gag 1311 Pro Leu Leu Ala Ala Leu Lys Ala Gly HisTrp Val Val Leu Asp Glu 80 85 90 ctt aac ctg gct tct cag tct gta ttg gaagga ctc aat gct tgt ttt 1359 Leu Asn Leu Ala Ser Gln Ser Val Leu Glu GlyLeu Asn Ala Cys Phe 95 100 105 gac cac cga gga gaa atc tat gtg cct gagtta gga atg agc ttt caa 1407 Asp His Arg Gly Glu Ile Tyr Val Pro Glu LeuGly Met Ser Phe Gln 110 115 120 gtg cag cat gaa aag acg aag att ttt gggtgt cag aat ccc ttt aga 1455 Val Gln His Glu Lys Thr Lys Ile Phe Gly CysGln Asn Pro Phe Arg 125 130 135 caa gga ggt ggg agg aaa ggc ttg ccc aggtct ttc ctt aac aga ttc 1503 Gln Gly Gly Gly Arg Lys Gly Leu Pro Arg SerPhe Leu Asn Arg Phe 140 145 150 155 act cag gtc ttc gtt gat ccc ctt acagta att gac atg gag ttc att 1551 Thr Gln Val Phe Val Asp Pro Leu Thr ValIle Asp Met Glu Phe Ile 160 165 170 gcc agt act ttg ttt cca gcc att gagaaa aat att gtt aag aaa atg 1599 Ala Ser Thr Leu Phe Pro Ala Ile Glu LysAsn Ile Val Lys Lys Met 175 180 185 gtt gct ttc aat aac caa att gat catgaa gtg act gtt gag aag aaa 1647 Val Ala Phe Asn Asn Gln Ile Asp His GluVal Thr Val Glu Lys Lys 190 195 200 tgg ggg caa aaa gga gga ccc tgg gaattc aac ctc cgg gac ctt ttc 1695 Trp Gly Gln Lys Gly Gly Pro Trp Glu PheAsn Leu Arg Asp Leu Phe 205 210 215 cgc tgg tgt cag ttg atg ctg gtt gaccag tcc cct ggg tgt tat gat 1743 Arg Trp Cys Gln Leu Met Leu Val Asp GlnSer Pro Gly Cys Tyr Asp 220 225 230 235 cct ggt cag cat gtg ttt ttg gtctat ggt gaa aga atg aga acc gaa 1791 Pro Gly Gln His Val Phe Leu Val TyrGly Glu Arg Met Arg Thr Glu 240 245 250 gag gac aaa aaa aag gtc att gctgta ttc aag gat gtg ttt ggt tca 1839 Glu Asp Lys Lys Lys Val Ile Ala ValPhe Lys Asp Val Phe Gly Ser 255 260 265 aat tcc aac cca tac atg gga accaga cta ttt cgt atc act ccc tat 1887 Asn Ser Asn Pro Tyr Met Gly Thr ArgLeu Phe Arg Ile Thr Pro Tyr 270 275 280 gat gtt cag ttg ggc tac tca gtcctt tcc cgt ggg agc tgt gtt cct 1935 Asp Val Gln Leu Gly Tyr Ser Val LeuSer Arg Gly Ser Cys Val Pro 285 290 295 cac ccg tcc cgc cat ccc ctg ttgctc ctg cac cag tca ttc caa ccc 1983 His Pro Ser Arg His Pro Leu Leu LeuLeu His Gln Ser Phe Gln Pro 300 305 310 315 ctg gag tca atc atg aag tgtgtg cag atg agc tgg atg gtc atc ctg 2031 Leu Glu Ser Ile Met Lys Cys ValGln Met Ser Trp Met Val Ile Leu 320 325 330 gtc ggg cca gcc tct gtg ggcaag acc agc ctg gtc cag ctt ctg gca 2079 Val Gly Pro Ala Ser Val Gly LysThr Ser Leu Val Gln Leu Leu Ala 335 340 345 cac ctt act ggc cac aca ttaaag atc atg gct atg aac agt gca atg 2127 His Leu Thr Gly His Thr Leu LysIle Met Ala Met Asn Ser Ala Met 350 355 360 gat act act gag ctg ctg ggtgga ttt gag cag gtt gat ctt ata cga 2175 Asp Thr Thr Glu Leu Leu Gly GlyPhe Glu Gln Val Asp Leu Ile Arg 365 370 375 cct tgg agg agg ctg cta gagaag gtg gag gga act gta agg gca ctg 2223 Pro Trp Arg Arg Leu Leu Glu LysVal Glu Gly Thr Val Arg Ala Leu 380 385 390 395 tta agg gat agc ctc cttatc agt gct gat gat gca gaa gta gtg ctg 2271 Leu Arg Asp Ser Leu Leu IleSer Ala Asp Asp Ala Glu Val Val Leu 400 405 410 cga gcc tgg agt cat tttctt ctg aca tat aag cct aag tgt ctt gga 2319 Arg Ala Trp Ser His Phe LeuLeu Thr Tyr Lys Pro Lys Cys Leu Gly 415 420 425 gaa ggt ggt aaa gct atcacg atg gag att gtc aac aaa cta gaa gca 2367 Glu Gly Gly Lys Ala Ile ThrMet Glu Ile Val Asn Lys Leu Glu Ala 430 435 440 gtg tta ttg ctt atg cagcga ctc aac aat aaa atc aac tca tac tgc 2415 Val Leu Leu Leu Met Gln ArgLeu Asn Asn Lys Ile Asn Ser Tyr Cys 445 450 455 aag gca gag ttt gcc aaactt gtt gaa gag ttc cga agc ttt ggt gtg 2463 Lys Ala Glu Phe Ala Lys LeuVal Glu Glu Phe Arg Ser Phe Gly Val 460 465 470 475 aag ctt acg cag ttggcc agt ggc cat agc cat ggc aca ttt gaa tgg 2511 Lys Leu Thr Gln Leu AlaSer Gly His Ser His Gly Thr Phe Glu Trp 480 485 490 gtt gac agc atg ttggtt cag gcc ctg aag tct gga gac tgg ctt ctg 2559 Val Asp Ser Met Leu ValGln Ala Leu Lys Ser Gly Asp Trp Leu Leu 495 500 505 atg gac aat gtt aacttc tgc aac cca tca gtg ttg gat cgt ttg aat 2607 Met Asp Asn Val Asn PheCys Asn Pro Ser Val Leu Asp Arg Leu Asn 510 515 520 gct ttg ctt gaa cccgga ggt gtc ctc act att agt gag aga gga atg 2655 Ala Leu Leu Glu Pro GlyGly Val Leu Thr Ile Ser Glu Arg Gly Met 525 530 535 ata gat gga tcc actccc acg ata aca cca aat ccc aat ttc aga ctt 2703 Ile Asp Gly Ser Thr ProThr Ile Thr Pro Asn Pro Asn Phe Arg Leu 540 545 550 555 ttc ctc tcg atggat cct gtt cat gga gat ata tcc cga gct atg agg 2751 Phe Leu Ser Met AspPro Val His Gly Asp Ile Ser Arg Ala Met Arg 560 565 570 aat cgt gga cttgaa atc tac att tca ggg gaa ggg gat gca agc acc 2799 Asn Arg Gly Leu GluIle Tyr Ile Ser Gly Glu Gly Asp Ala Ser Thr 575 580 585 cca gac aac ctggat ttg aaa gtt ctg ctg cac agc ctt gga ttg gtg 2847 Pro Asp Asn Leu AspLeu Lys Val Leu Leu His Ser Leu Gly Leu Val 590 595 600 ggg aac agt gtatgt gac atc ctc ttg gct tta cac aca gag acc cgg 2895 Gly Asn Ser Val CysAsp Ile Leu Leu Ala Leu His Thr Glu Thr Arg 605 610 615 agc act gtt gtaggt tct cca aca tct tct gta tca act cta atc cag 2943 Ser Thr Val Val GlySer Pro Thr Ser Ser Val Ser Thr Leu Ile Gln 620 625 630 635 aca gcc atacta att gtc cag tac ctg cag cga ggg ctg agt tta gac 2991 Thr Ala Ile LeuIle Val Gln Tyr Leu Gln Arg Gly Leu Ser Leu Asp 640 645 650 aga gcc ttttct gaa gca tgc tgg gaa gta tat gtc tgt tcc cag cat 3039 Arg Ala Phe SerGlu Ala Cys Trp Glu Val Tyr Val Cys Ser Gln His 655 660 665 tca cca gcaaac cgg aag ctt gta cag gct tta ctg gag aaa cat gtt 3087 Ser Pro Ala AsnArg Lys Leu Val Gln Ala Leu Leu Glu Lys His Val 670 675 680 tct tct ttgcga gca cat gaa acc tgg gga gac tcc att ctt ggc atg 3135 Ser Ser Leu ArgAla His Glu Thr Trp Gly Asp Ser Ile Leu Gly Met 685 690 695 gga ctg tggcca gat tct gtg ccc tca gct ctc ttt gct act gaa gat 3183 Gly Leu Trp ProAsp Ser Val Pro Ser Ala Leu Phe Ala Thr Glu Asp 700 705 710 715 tca cacctg tct aca gtc cga aga gat gga cag atc tta gta tat tgt 3231 Ser His LeuSer Thr Val Arg Arg Asp Gly Gln Ile Leu Val Tyr Cys 720 725 730 ctc aacagg atg agc atg aaa acc agc agc tgg aca agg agt cag cct 3279 Leu Asn ArgMet Ser Met Lys Thr Ser Ser Trp Thr Arg Ser Gln Pro 735 740 745 ttt accttg caa gac tta gag aaa att atg cag tcc ccc agc cct gag 3327 Phe Thr LeuGln Asp Leu Glu Lys Ile Met Gln Ser Pro Ser Pro Glu 750 755 760 aac ctgaaa ttc aat gca gtc gaa gtg aat act tac tgg atc gat gaa 3375 Asn Leu LysPhe Asn Ala Val Glu Val Asn Thr Tyr Trp Ile Asp Glu 765 770 775 cca gatgtt ttg gtc atg gct gtt aaa ttg ctc ata gaa aga gca acc 3423 Pro Asp ValLeu Val Met Ala Val Lys Leu Leu Ile Glu Arg Ala Thr 780 785 790 795 aatcag gat tgg atg ctc aga gtt aaa tgg ctt tat cat tta gcc aag 3471 Asn GlnAsp Trp Met Leu Arg Val Lys Trp Leu Tyr His Leu Ala Lys 800 805 810 aatata ccg cag ggg ctt gag tcc ata caa att cat ttg gaa gcc agt 3519 Asn IlePro Gln Gly Leu Glu Ser Ile Gln Ile His Leu Glu Ala Ser 815 820 825 gctgca tct ctc agg aat ttt tac tca cat tcc ctc tca ggt gca gtc 3567 Ala AlaSer Leu Arg Asn Phe Tyr Ser His Ser Leu Ser Gly Ala Val 830 835 840 agtaat gtt ttc aaa ata tta caa cca aat aca aca gat gaa ttt gtg 3615 Ser AsnVal Phe Lys Ile Leu Gln Pro Asn Thr Thr Asp Glu Phe Val 845 850 855 atccct ctg gat ccc cga tgg aat atg cag gct ctg gac atg att aga 3663 Ile ProLeu Asp Pro Arg Trp Asn Met Gln Ala Leu Asp Met Ile Arg 860 865 870 875aat ttg atg gac ttt gac cca caa aca gac cag cct gac cag ctc ttt 3711 AsnLeu Met Asp Phe Asp Pro Gln Thr Asp Gln Pro Asp Gln Leu Phe 880 885 890gcc ctt tta gaa tca gct gca aac aag aca atc ata tat ctt gac cgg 3759 AlaLeu Leu Glu Ser Ala Ala Asn Lys Thr Ile Ile Tyr Leu Asp Arg 895 900 905gaa aaa cgg gtt ttt act gaa gca aat ttg gtt tct gtt ggt agc aaa 3807 GluLys Arg Val Phe Thr Glu Ala Asn Leu Val Ser Val Gly Ser Lys 910 915 920aag cta aga gag agt gtt ttg aga atg tcc ttt gaa ttc cat caa gat 3855 LysLeu Arg Glu Ser Val Leu Arg Met Ser Phe Glu Phe His Gln Asp 925 930 935cca gaa agc tat cac act ctg ccc cat gaa att gtg gtc aat ctt gct 3903 ProGlu Ser Tyr His Thr Leu Pro His Glu Ile Val Val Asn Leu Ala 940 945 950955 gct ttt ttt gaa ctt tgt gat gca cta gtc ctg ctc tgg gta cag tcc 3951Ala Phe Phe Glu Leu Cys Asp Ala Leu Val Leu Leu Trp Val Gln Ser 960 965970 tcc cag gga atg gtg tct gat gcc agt gcc aat gag atc tta ggt tct 3999Ser Gln Gly Met Val Ser Asp Ala Ser Ala Asn Glu Ile Leu Gly Ser 975 980985 ctg cgg tgg cgg gac cgg ttc tgg act gtg gcc gac aca gta aaa gta 4047Leu Arg Trp Arg Asp Arg Phe Trp Thr Val Ala Asp Thr Val Lys Val 990 9951000 gat gcc cca ggt ctg gcc ctt ctt gcc ctc cat tgg cac tgg gtt 4092Asp Ala Pro Gly Leu Ala Leu Leu Ala Leu His Trp His Trp Val 1005 10101015 tta aaa cat ctg gtc cac cag atc ccc cga ctt ctg atg aat tat 4137Leu Lys His Leu Val His Gln Ile Pro Arg Leu Leu Met Asn Tyr 1020 10251030 gaa gac aaa tat tac aaa gaa gtt cag act gtc tca gaa cat att 4182Glu Asp Lys Tyr Tyr Lys Glu Val Gln Thr Val Ser Glu His Ile 1035 10401045 cag aat tgt ctg ggg agc cag act ggt ggc ttc gct ggt ata aag 4227Gln Asn Cys Leu Gly Ser Gln Thr Gly Gly Phe Ala Gly Ile Lys 1050 10551060 aag ttg cag aag ttc ctg gga cga ccg ttt cct ttt aag gac aag 4272Lys Leu Gln Lys Phe Leu Gly Arg Pro Phe Pro Phe Lys Asp Lys 1065 10701075 ctg gtg gtg gag tgt ttt tca caa ctg aag gtc ctt aac aaa gtc 4317Leu Val Val Glu Cys Phe Ser Gln Leu Lys Val Leu Asn Lys Val 1080 10851090 ctt gcc atc agg gag cag atg tct gcc ctt ggg gag agt gga tgg 4362Leu Ala Ile Arg Glu Gln Met Ser Ala Leu Gly Glu Ser Gly Trp 1095 11001105 cag gaa gac att aac cgt ctc caa gtg gtt gct tct cag tgg aca 4407Gln Glu Asp Ile Asn Arg Leu Gln Val Val Ala Ser Gln Trp Thr 1110 11151120 tta aag aaa agt ctc ctg caa gcc tgg gga ctg atc ctc aga gca 4452Leu Lys Lys Ser Leu Leu Gln Ala Trp Gly Leu Ile Leu Arg Ala 1125 11301135 aat att ttg gaa gat gtc agc cta gat gaa ttg aag aat ttt gtg 4497Asn Ile Leu Glu Asp Val Ser Leu Asp Glu Leu Lys Asn Phe Val 1140 11451150 cat gct cag tgt tta gaa ctg aaa gcc aaa gga ctc tca ctt ggt 4542His Ala Gln Cys Leu Glu Leu Lys Ala Lys Gly Leu Ser Leu Gly 1155 11601165 ttt ctg gag aaa aag cat gat gaa gct tcc tcc ctg tcc cat cca 4587Phe Leu Glu Lys Lys His Asp Glu Ala Ser Ser Leu Ser His Pro 1170 11751180 gac ttg acc tcc gta atc cac ctc acc agg agt gtt cag ttg tgg 4632Asp Leu Thr Ser Val Ile His Leu Thr Arg Ser Val Gln Leu Trp 1185 11901195 cct gca atg gag tac ctg gct atg ctt tgg cgg tac aaa gtg aca 4677Pro Ala Met Glu Tyr Leu Ala Met Leu Trp Arg Tyr Lys Val Thr 1200 12051210 gct gat ttt atg gca caa gct tgt ctc aga aga tgc agc aaa aat 4722Ala Asp Phe Met Ala Gln Ala Cys Leu Arg Arg Cys Ser Lys Asn 1215 12201225 caa caa ccc cag ata aat gag gag ata agt cac ctc atc tca ttt 4767Gln Gln Pro Gln Ile Asn Glu Glu Ile Ser His Leu Ile Ser Phe 1230 12351240 tgt ctt tat cac aca cct gtt aca cct caa gag ctt cga gat ctg 4812Cys Leu Tyr His Thr Pro Val Thr Pro Gln Glu Leu Arg Asp Leu 1245 12501255 tgg tcc ttg ctg cat cat cag aag gtg tct cct gaa gaa att aca 4857Trp Ser Leu Leu His His Gln Lys Val Ser Pro Glu Glu Ile Thr 1260 12651270 tct ttg tgg tcc gag tta ttt aat tcc atg ttt atg tct ttc tgg 4902Ser Leu Trp Ser Glu Leu Phe Asn Ser Met Phe Met Ser Phe Trp 1275 12801285 agc agt act gtg acc aca aat cca gag tac tgg cta atg tgg aac 4947Ser Ser Thr Val Thr Thr Asn Pro Glu Tyr Trp Leu Met Trp Asn 1290 12951300 cct ttg cct ggt atg cag cag agg gag gca ccc aag tct gtt ttg 4992Pro Leu Pro Gly Met Gln Gln Arg Glu Ala Pro Lys Ser Val Leu 1305 13101315 gac tcc aca ttg aag ggc ccc ggc aat ctc aat aga ccc ata ttc 5037Asp Ser Thr Leu Lys Gly Pro Gly Asn Leu Asn Arg Pro Ile Phe 1320 13251330 tct aag tgc tgc ttt gaa gtc tta acc agc agc tgg aga gca agt 5082Ser Lys Cys Cys Phe Glu Val Leu Thr Ser Ser Trp Arg Ala Ser 1335 13401345 ccc tgg gat gtg agt ggc ctc ccc att ctt tcc tcc tct cac gtg 5127Pro Trp Asp Val Ser Gly Leu Pro Ile Leu Ser Ser Ser His Val 1350 13551360 acc cta gga gag tgg gtt gag aga act cag cag ctc cag gac atc 5172Thr Leu Gly Glu Trp Val Glu Arg Thr Gln Gln Leu Gln Asp Ile 1365 13701375 agt tcg atg ctt tgg act aac atg gct atc tct tca gta gca gaa 5217Ser Ser Met Leu Trp Thr Asn Met Ala Ile Ser Ser Val Ala Glu 1380 13851390 ttc aga cgc acg gat tcc caa ctc cag ggg cag gtg ctg ttc cgg 5262Phe Arg Arg Thr Asp Ser Gln Leu Gln Gly Gln Val Leu Phe Arg 1395 14001405 cac ctg gca ggc cta gca gag ctg ctc cca gag tcc cgg cgg cag 5307His Leu Ala Gly Leu Ala Glu Leu Leu Pro Glu Ser Arg Arg Gln 1410 14151420 gag tac atg cag aac tgt gag cag ctg ctg ctt ggg agc agc cag 5352Glu Tyr Met Gln Asn Cys Glu Gln Leu Leu Leu Gly Ser Ser Gln 1425 14301435 gcc ttc cag cat gtg ggc cag aca ctt ggg gac atg gct ggt cag 5397Ala Phe Gln His Val Gly Gln Thr Leu Gly Asp Met Ala Gly Gln 1440 14451450 gag gtg ctg ccc aag gaa ctg ctc tgc cag ttg ctc acc tcc ctg 5442Glu Val Leu Pro Lys Glu Leu Leu Cys Gln Leu Leu Thr Ser Leu 1455 14601465 cac cac ttt gtt ggt gaa ggg gag agt aag agg agc ctg cct gag 5487His His Phe Val Gly Glu Gly Glu Ser Lys Arg Ser Leu Pro Glu 1470 14751480 cca gcc cag cgt ggg agc ctc tgg gtg agc ctc ggc ttg ctc cag 5532Pro Ala Gln Arg Gly Ser Leu Trp Val Ser Leu Gly Leu Leu Gln 1485 14901495 att cag aca tgg ctt ccc cag gca cgc ttt gac cct gcg gtg aag 5577Ile Gln Thr Trp Leu Pro Gln Ala Arg Phe Asp Pro Ala Val Lys 1500 15051510 agg gag tac aag ctc aat tac gtc aag gaa gag tta cac caa ctg 5622Arg Glu Tyr Lys Leu Asn Tyr Val Lys Glu Glu Leu His Gln Leu 1515 15201525 cag tgt gaa tgg aag acc cgg aac ctg tca tcc cag ctg cag act 5667Gln Cys Glu Trp Lys Thr Arg Asn Leu Ser Ser Gln Leu Gln Thr 1530 15351540 gga aga gac ctg gaa gat gaa gtc gtt gtc agc tac tct cat cct 5712Gly Arg Asp Leu Glu Asp Glu Val Val Val Ser Tyr Ser His Pro 1545 15501555 cac gtc agg ctg ctt cgc caa agg atg gat cgg ctg gat aat tta 5757His Val Arg Leu Leu Arg Gln Arg Met Asp Arg Leu Asp Asn Leu 1560 15651570 acc tgt cac ctg ttg aag aaa cag gcc ttt aga ccc cag ctg cct 5802Thr Cys His Leu Leu Lys Lys Gln Ala Phe Arg Pro Gln Leu Pro 1575 15801585 gcc tac gag tcc ctg gtt cag gag atc cac cac tac gtc acc agc 5847Ala Tyr Glu Ser Leu Val Gln Glu Ile His His Tyr Val Thr Ser 1590 15951600 atc gcc aag gcc cct gct gtt cag gat ctg ctc aca cgg ctt ctg 5892Ile Ala Lys Ala Pro Ala Val Gln Asp Leu Leu Thr Arg Leu Leu 1605 16101615 cag gcc ctc cac ata gat ggg cca cgg tct gcc caa gta gcc cag 5937Gln Ala Leu His Ile Asp Gly Pro Arg Ser Ala Gln Val Ala Gln 1620 16251630 agc ctt cta aag gag gag gcc tct tgg cag cag tca cac cac cag 5982Ser Leu Leu Lys Glu Glu Ala Ser Trp Gln Gln Ser His His Gln 1635 16401645 ttc cgg aag cgg ctg tca gag gag tac acc ttc tat cca gat gcc 6027Phe Arg Lys Arg Leu Ser Glu Glu Tyr Thr Phe Tyr Pro Asp Ala 1650 16551660 gtg agc cca ctg cag gca tcc ata ttg cag tta caa cat ggc atg 6072Val Ser Pro Leu Gln Ala Ser Ile Leu Gln Leu Gln His Gly Met 1665 16701675 agg ctg gtg gcc tct gag ctc cac acc tca ctc tac agc agt atg 6117Arg Leu Val Ala Ser Glu Leu His Thr Ser Leu Tyr Ser Ser Met 1680 16851690 gtt ggt gca gac agg ctg ggg acc ctg gcc aca gcc ttg ctg gct 6162Val Gly Ala Asp Arg Leu Gly Thr Leu Ala Thr Ala Leu Leu Ala 1695 17001705 ttc cca tcg gtg ggc ccc acc ttc ccg act tac tat gct cat gca 6207Phe Pro Ser Val Gly Pro Thr Phe Pro Thr Tyr Tyr Ala His Ala 1710 17151720 gac act ttg tgc tcg gtg aag tct gag gag gtt cta cga ggc ctt 6252Asp Thr Leu Cys Ser Val Lys Ser Glu Glu Val Leu Arg Gly Leu 1725 17301735 ggg aag cta atc ctc aag cgc tca gga gga aag gag ctg gaa ggc 6297Gly Lys Leu Ile Leu Lys Arg Ser Gly Gly Lys Glu Leu Glu Gly 1740 17451750 aag ggc cag aaa gcc tgt ccc act cgg gag cag ctg ctg atg aat 6342Lys Gly Gln Lys Ala Cys Pro Thr Arg Glu Gln Leu Leu Met Asn 1755 17601765 gct ctc ctt tac ctg cgc tcc cac gtg tta tgc aag gga gag ttg 6387Ala Leu Leu Tyr Leu Arg Ser His Val Leu Cys Lys Gly Glu Leu 1770 17751780 gac cag agg gcc ctg cag ctc ttc aga cat gtg tgt cag gaa atc 6432Asp Gln Arg Ala Leu Gln Leu Phe Arg His Val Cys Gln Glu Ile 1785 17901795 atc agt gag tgg gat gag cag gaa cgc ata gcc caa gag aag gct 6477Ile Ser Glu Trp Asp Glu Gln Glu Arg Ile Ala Gln Glu Lys Ala 1800 18051810 gag cag gaa agc ggc ctg tat aga tac agg agc agg aac tct agg 6522Glu Gln Glu Ser Gly Leu Tyr Arg Tyr Arg Ser Arg Asn Ser Arg 1815 18201825 aca gcc ctg agt gaa gag gag gag gaa gaa cgg gag ttc aga aaa 6567Thr Ala Leu Ser Glu Glu Glu Glu Glu Glu Arg Glu Phe Arg Lys 1830 18351840 cag ttc ccc ctg cat gaa aag gac ttt gca gat att ttg gtg cag 6612Gln Phe Pro Leu His Glu Lys Asp Phe Ala Asp Ile Leu Val Gln 1845 18501855 cca acg ttg gag gag aac aaa gga act tca gat ggg caa gaa gag 6657Pro Thr Leu Glu Glu Asn Lys Gly Thr Ser Asp Gly Gln Glu Glu 1860 18651870 gaa gca ggc aca aac cca gct ctc ctc tcc cag aat tca atg cag 6702Glu Ala Gly Thr Asn Pro Ala Leu Leu Ser Gln Asn Ser Met Gln 1875 18801885 gca gta atg ctg ata cac cag caa ttg tgt ctc aac ttt gct cga 6747Ala Val Met Leu Ile His Gln Gln Leu Cys Leu Asn Phe Ala Arg 1890 18951900 tcc ctc tgg tat caa cag act ctg ccg cca cat gaa gca aag cat 6792Ser Leu Trp Tyr Gln Gln Thr Leu Pro Pro His Glu Ala Lys His 1905 19101915 tac ctc agc ctg ttt ctg tct tgc tat cag act ggg gca tcg ctt 6837Tyr Leu Ser Leu Phe Leu Ser Cys Tyr Gln Thr Gly Ala Ser Leu 1920 19251930 gtg aca cac ttc tac ccc ctg atg gga gtt gaa ctg aat gac cga 6882Val Thr His Phe Tyr Pro Leu Met Gly Val Glu Leu Asn Asp Arg 1935 19401945 ctc ttg ggc agc caa ctt ttg gcc tgt acc ctc tcc cat aac act 6927Leu Leu Gly Ser Gln Leu Leu Ala Cys Thr Leu Ser His Asn Thr 1950 19551960 ctt ttt ggg gag gca ccc tca gac ctg atg gtg aaa cct gat ggg 6972Leu Phe Gly Glu Ala Pro Ser Asp Leu Met Val Lys Pro Asp Gly 1965 19701975 ccc tat gac ttc tac cag cat ccc aat gtt cca gaa gca cgg cag 7017Pro Tyr Asp Phe Tyr Gln His Pro Asn Val Pro Glu Ala Arg Gln 1980 19851990 tgt caa cct gtg ctt caa ggt ttc tca gag gct gtc agt cac ttg 7062Cys Gln Pro Val Leu Gln Gly Phe Ser Glu Ala Val Ser His Leu 1995 20002005 cta cag gac tgg cca gaa cac cca gcg ctt gaa cag ctc ctg gtt 7107Leu Gln Asp Trp Pro Glu His Pro Ala Leu Glu Gln Leu Leu Val 2010 20152020 gta atg gac aga att cgt agt ttc cca ctt tcc agt ccc atc tca 7152Val Met Asp Arg Ile Arg Ser Phe Pro Leu Ser Ser Pro Ile Ser 2025 20302035 aag ttc ctg aat ggc tta gag atc ctt ctg gca aag gca cag gat 7197Lys Phe Leu Asn Gly Leu Glu Ile Leu Leu Ala Lys Ala Gln Asp 2040 20452050 tgg gag gaa aat gca agt cga gct ttg tct ttg cgg aaa cat ctt 7242Trp Glu Glu Asn Ala Ser Arg Ala Leu Ser Leu Arg Lys His Leu 2055 20602065 gat ttg atc agt cag atg atc att cgg tgg cgt aaa ctg gag ctg 7287Asp Leu Ile Ser Gln Met Ile Ile Arg Trp Arg Lys Leu Glu Leu 2070 20752080 aac tgc tgg tcc atg agt ttg gat aat act atg aag cgc cac acc 7332Asn Cys Trp Ser Met Ser Leu Asp Asn Thr Met Lys Arg His Thr 2085 20902095 gag aaa tcc acc aag cac tgg ttc tcc atc tat cag atg ctt gag 7377Glu Lys Ser Thr Lys His Trp Phe Ser Ile Tyr Gln Met Leu Glu 2100 21052110 aag cac atg cag gaa caa aca gaa gaa cag gaa gat gac aaa cag 7422Lys His Met Gln Glu Gln Thr Glu Glu Gln Glu Asp Asp Lys Gln 2115 21202125 atg acc ttg atg ttg ctg gtc agc aca tta caa gca ttt att gaa 7467Met Thr Leu Met Leu Leu Val Ser Thr Leu Gln Ala Phe Ile Glu 2130 21352140 gga tcc tcg ctg gga gag ttc cat gtg cga ctt cag atg tta ctg 7512Gly Ser Ser Leu Gly Glu Phe His Val Arg Leu Gln Met Leu Leu 2145 21502155 gtt ttc cat tgt cat gtc ttg ctg atg cca cag gtt gaa gga aag 7557Val Phe His Cys His Val Leu Leu Met Pro Gln Val Glu Gly Lys 2160 21652170 gat tca ctt tgc agt gtt cta tgg aat ttg tac cat tat tac aag 7602Asp Ser Leu Cys Ser Val Leu Trp Asn Leu Tyr His Tyr Tyr Lys 2175 21802185 caa ttc ttt gac cgg gtc cag gcc aaa att gtg gaa ctt cgt tcc 7647Gln Phe Phe Asp Arg Val Gln Ala Lys Ile Val Glu Leu Arg Ser 2190 21952200 ccc cta gaa aaa gaa ctt aaa gaa ttt gtt aag att tcc aag tgg 7692Pro Leu Glu Lys Glu Leu Lys Glu Phe Val Lys Ile Ser Lys Trp 2205 22102215 aat gat gtc agc ttc tgg tcc att aag caa tct gta gaa aag aca 7737Asn Asp Val Ser Phe Trp Ser Ile Lys Gln Ser Val Glu Lys Thr 2220 22252230 cac agg aca ctc ttt aaa ttc atg aag aaa ttt gaa gca gtc ctg 7782His Arg Thr Leu Phe Lys Phe Met Lys Lys Phe Glu Ala Val Leu 2235 22402245 agt gaa ccc tgc cgg tca tcc ctg gtg gag agt gac aag gaa gaa 7827Ser Glu Pro Cys Arg Ser Ser Leu Val Glu Ser Asp Lys Glu Glu 2250 22552260 cag cct gac ttt ttg ccc agg cca aca gat gga gct gca agt gaa 7872Gln Pro Asp Phe Leu Pro Arg Pro Thr Asp Gly Ala Ala Ser Glu 2265 22702275 ctg tct tcc att cag aat ctg aac agg gca ctg agg gag acc ctg 7917Leu Ser Ser Ile Gln Asn Leu Asn Arg Ala Leu Arg Glu Thr Leu 2280 22852290 tta gcc caa cca gca gct ggg cag gcc aca att cca gag tgg tgt 7962Leu Ala Gln Pro Ala Ala Gly Gln Ala Thr Ile Pro Glu Trp Cys 2295 23002305 cag ggc gct gct cct tcc ggc ttg gaa ggg gag ctt ctg cgt cgc 8007Gln Gly Ala Ala Pro Ser Gly Leu Glu Gly Glu Leu Leu Arg Arg 2310 23152320 ttg cca aag ctc agg aaa cgc atg agg aag atg tgc ctg acg ttc 8052Leu Pro Lys Leu Arg Lys Arg Met Arg Lys Met Cys Leu Thr Phe 2325 23302335 atg aag gag agc ccc ctg cct cgc ctt gtg gag ggc ctt gat cag 8097Met Lys Glu Ser Pro Leu Pro Arg Leu Val Glu Gly Leu Asp Gln 2340 23452350 ttc aca ggt gaa gtg att tcc tct gtg agt gag ctg cag agc tta 8142Phe Thr Gly Glu Val Ile Ser Ser Val Ser Glu Leu Gln Ser Leu 2355 23602365 aag gtg gaa ccc tct gca gag aag gag aag cag cgg tca gaa gcc 8187Lys Val Glu Pro Ser Ala Glu Lys Glu Lys Gln Arg Ser Glu Ala 2370 23752380 aag cac att ctc atg caa aaa cag cga gct ttg tca gac ctc ttt 8232Lys His Ile Leu Met Gln Lys Gln Arg Ala Leu Ser Asp Leu Phe 2385 23902395 aaa cac ctt gca aaa att ggt ttg tcg tat cgc aaa ggt ctt gct 8277Lys His Leu Ala Lys Ile Gly Leu Ser Tyr Arg Lys Gly Leu Ala 2400 24052410 tgg gcc cgt tca aaa aac cct caa gag atg ctt cat ctt cac cca 8322Trp Ala Arg Ser Lys Asn Pro Gln Glu Met Leu His Leu His Pro 2415 24202425 tta gat ctc cag agc gca ttg tcc atc gtc agc agc act cag gag 8367Leu Asp Leu Gln Ser Ala Leu Ser Ile Val Ser Ser Thr Gln Glu 2430 24352440 gct gat tct agg ctg ctt aca gaa atc tcg tct tca tgg gat gga 8412Ala Asp Ser Arg Leu Leu Thr Glu Ile Ser Ser Ser Trp Asp Gly 2445 24502455 tgc cag aag tat ttt tat cgc tct ctt gca cgg cat gcc agg ctt 8457Cys Gln Lys Tyr Phe Tyr Arg Ser Leu Ala Arg His Ala Arg Leu 2460 24652470 aac gca gca cta gca act cct gcc aag gaa atg ggc atg ggc aac 8502Asn Ala Ala Leu Ala Thr Pro Ala Lys Glu Met Gly Met Gly Asn 2475 24802485 gtg gag agg tgc aga ggg ttc tca gca cat ttg atg aag atg ctc 8547Val Glu Arg Cys Arg Gly Phe Ser Ala His Leu Met Lys Met Leu 2490 24952500 gtc cga cag cgg cgc tcc ctg acc acg ctc agt gag cag tgg atc 8592Val Arg Gln Arg Arg Ser Leu Thr Thr Leu Ser Glu Gln Trp Ile 2505 25102515 atc ctc agg aac ctc ctc agc tgt gtg caa gag att cac agc agg 8637Ile Leu Arg Asn Leu Leu Ser Cys Val Gln Glu Ile His Ser Arg 2520 25252530 ctg atg ggg ccc cag gcc tac ccc gtg gcc ttc ccc cct cag gat 8682Leu Met Gly Pro Gln Ala Tyr Pro Val Ala Phe Pro Pro Gln Asp 2535 25402545 ggc gtg cag cag tgg aca gag cgc ctg cag cac ctg gcc atg cag 8727Gly Val Gln Gln Trp Thr Glu Arg Leu Gln His Leu Ala Met Gln 2550 25552560 tgc cag atc ctg ctt gag cag ctc tcc tgg ctc ctc cag tgc tgc 8772Cys Gln Ile Leu Leu Glu Gln Leu Ser Trp Leu Leu Gln Cys Cys 2565 25702575 ccc agt gta ggg cca gct cca ggc cat ggc aat gtc cag gta ctg 8817Pro Ser Val Gly Pro Ala Pro Gly His Gly Asn Val Gln Val Leu 2580 25852590 ggg cag cct cct ggc ccc tgc ctg gaa gga cca gaa ctt agc aag 8862Gly Gln Pro Pro Gly Pro Cys Leu Glu Gly Pro Glu Leu Ser Lys 2595 26002605 gga caa ctt tgt gga gta gtg ctg gac cta att cct tcc aat ctg 8907Gly Gln Leu Cys Gly Val Val Leu Asp Leu Ile Pro Ser Asn Leu 2610 26152620 agc tac cca tct cca ata cct gga agt cag ctg ccc tct ggt tgc 8952Ser Tyr Pro Ser Pro Ile Pro Gly Ser Gln Leu Pro Ser Gly Cys 2625 26302635 cgg atg cgg aaa cag gat cac ctt tgg caa cag tca act acg aga 8997Arg Met Arg Lys Gln Asp His Leu Trp Gln Gln Ser Thr Thr Arg 2640 26452650 tta aca gag atg cta aaa acc att aaa aca gtg aaa gct gac gtc 9042Leu Thr Glu Met Leu Lys Thr Ile Lys Thr Val Lys Ala Asp Val 2655 26602665 gac aaa att aga cag cag tct tgt gag act ctc ttt cat tct tgg 9087Asp Lys Ile Arg Gln Gln Ser Cys Glu Thr Leu Phe His Ser Trp 2670 26752680 aaa gat ttt gaa gtt tgc tct tct gcg ctg agt tgc ttg tcc cag 9132Lys Asp Phe Glu Val Cys Ser Ser Ala Leu Ser Cys Leu Ser Gln 2685 26902695 gtg tca gtt cat ttg cag ggc cta gag tcc ttg ttc att ctt cca 9177Val Ser Val His Leu Gln Gly Leu Glu Ser Leu Phe Ile Leu Pro 2700 27052710 ggg atg gag gtt gag caa aga gac tca caa atg gca cta gtt gaa 9222Gly Met Glu Val Glu Gln Arg Asp Ser Gln Met Ala Leu Val Glu 2715 27202725 agt ctg gaa tat gta aga gga gaa att agt aaa gcc atg gct gac 9267Ser Leu Glu Tyr Val Arg Gly Glu Ile Ser Lys Ala Met Ala Asp 2730 27352740 ttt act acc tgg aag acc cat ctg ctt act tca gat agc caa gga 9312Phe Thr Thr Trp Lys Thr His Leu Leu Thr Ser Asp Ser Gln Gly 2745 27502755 gga aat caa atg ttg gac gaa gga ttt gtg gaa gat ttt tca gag 9357Gly Asn Gln Met Leu Asp Glu Gly Phe Val Glu Asp Phe Ser Glu 2760 27652770 caa atg gaa att gcc atc cga gcc atc ctc tgt gcc atc cag aac 9402Gln Met Glu Ile Ala Ile Arg Ala Ile Leu Cys Ala Ile Gln Asn 2775 27802785 tta gaa gaa aga aag aat gaa aaa gca gag gag aac act gac caa 9447Leu Glu Glu Arg Lys Asn Glu Lys Ala Glu Glu Asn Thr Asp Gln 2790 27952800 gca agc cca caa gaa gat tat gca ggc ttt gag aga ctg caa tca 9492Ala Ser Pro Gln Glu Asp Tyr Ala Gly Phe Glu Arg Leu Gln Ser 2805 28102815 gga cat cta aca aaa ctc tta gag gat gac ttc tgg gcc gat gtg 9537Gly His Leu Thr Lys Leu Leu Glu Asp Asp Phe Trp Ala Asp Val 2820 28252830 agc act ttg cac gtg cag aaa ata att tct gcc atc tcc gag ctg 9582Ser Thr Leu His Val Gln Lys Ile Ile Ser Ala Ile Ser Glu Leu 2835 28402845 ttg gag agg ctg aaa tcg tac ggt gag gat ggc aca gca gca aag 9627Leu Glu Arg Leu Lys Ser Tyr Gly Glu Asp Gly Thr Ala Ala Lys 2850 28552860 cac ctg ttc ttc agc caa tcc tgt tcc ttg ctg gtg cgc ctg gtg 9672His Leu Phe Phe Ser Gln Ser Cys Ser Leu Leu Val Arg Leu Val 2865 28702875 ccg gtc ctc tcc agc tac tca gac ctc gtc ctc ttc ttc ctg acc 9717Pro Val Leu Ser Ser Tyr Ser Asp Leu Val Leu Phe Phe Leu Thr 2880 28852890 atg tct tta gca act cac cgt agt act gca aag ctg ctc tct gtg 9762Met Ser Leu Ala Thr His Arg Ser Thr Ala Lys Leu Leu Ser Val 2895 29002905 ctt gcc cag gtc ttt aca gag ctt gcc cag aag gga ttt tgc ttg 9807Leu Ala Gln Val Phe Thr Glu Leu Ala Gln Lys Gly Phe Cys Leu 2910 29152920 ccc aaa gaa ttt atg gaa gat tca gct gga gag gga gca act gag 9852Pro Lys Glu Phe Met Glu Asp Ser Ala Gly Glu Gly Ala Thr Glu 2925 29302935 ttc cat gac tat gag gga ggt gga att gga gaa ggc gag ggc atg 9897Phe His Asp Tyr Glu Gly Gly Gly Ile Gly Glu Gly Glu Gly Met 2940 29452950 aag gat gtg agt gac cag atc gga aat gaa gaa cag gtg gaa gat 9942Lys Asp Val Ser Asp Gln Ile Gly Asn Glu Glu Gln Val Glu Asp 2955 29602965 aca ttt cag aag ggt caa gaa aaa gac aaa gag gat cct gat tca 9987Thr Phe Gln Lys Gly Gln Glu Lys Asp Lys Glu Asp Pro Asp Ser 2970 29752980 aaa tct gat att aag ggc gag gat aat gcc att gag atg tcg gaa 10032Lys Ser Asp Ile Lys Gly Glu Asp Asn Ala Ile Glu Met Ser Glu 2985 29902995 gat ttt gat ggg aaa atg cat gat ggg gag ctt gaa gaa caa gaa 10077Asp Phe Asp Gly Lys Met His Asp Gly Glu Leu Glu Glu Gln Glu 3000 30053010 gag gat gat gag aaa tca gat agt gag ggc gga gac ctg gat aaa 10122Glu Asp Asp Glu Lys Ser Asp Ser Glu Gly Gly Asp Leu Asp Lys 3015 30203025 cac atg ggc gat ctc aat ggt gag gaa gct gac aaa cta gat gag 10167His Met Gly Asp Leu Asn Gly Glu Glu Ala Asp Lys Leu Asp Glu 3030 30353040 agg ctt tgg ggt gat gat gat gag gag gaa gat gag gag gaa gaa 10212Arg Leu Trp Gly Asp Asp Asp Glu Glu Glu Asp Glu Glu Glu Glu 3045 30503055 gac aat aaa act gaa gaa aca gga cca gga atg gat gag gaa gat 10257Asp Asn Lys Thr Glu Glu Thr Gly Pro Gly Met Asp Glu Glu Asp 3060 30653070 tct gaa ctt gtt gct aaa gat gac aac ttg gat agt ggc aat tca 10302Ser Glu Leu Val Ala Lys Asp Asp Asn Leu Asp Ser Gly Asn Ser 3075 30803085 aac aaa gat aaa agc cag caa gat aag aag gaa gaa aag gaa gaa 10347Asn Lys Asp Lys Ser Gln Gln Asp Lys Lys Glu Glu Lys Glu Glu 3090 30953100 gca gaa gct gat gat ggt gga caa ggt gaa gac aaa att aat gaa 10392Ala Glu Ala Asp Asp Gly Gly Gln Gly Glu Asp Lys Ile Asn Glu 3105 31103115 caa ata gat gag agg gac tat gat gaa aat gag gtg gac cct tac 10437Gln Ile Asp Glu Arg Asp Tyr Asp Glu Asn Glu Val Asp Pro Tyr 3120 31253130 cat ggc aat cag gaa aag gtg cca gaa ccc gag gct ttg gac ctt 10482His Gly Asn Gln Glu Lys Val Pro Glu Pro Glu Ala Leu Asp Leu 3135 31403145 cca gat gac ttg aac ctc gac agt gaa gac aag aat ggt ggt gag 10527Pro Asp Asp Leu Asn Leu Asp Ser Glu Asp Lys Asn Gly Gly Glu 3150 31553160 gac acc gac aat gaa gaa gga gaa gaa gag aat cct ttg gag ata 10572Asp Thr Asp Asn Glu Glu Gly Glu Glu Glu Asn Pro Leu Glu Ile 3165 31703175 aaa gaa aaa cca gaa gaa gca ggt cat gaa gct gag gaa aga gga 10617Lys Glu Lys Pro Glu Glu Ala Gly His Glu Ala Glu Glu Arg Gly 3180 31853190 gag acc gag acc gac cag aac gaa agt cag agt cca cag gag cct 10662Glu Thr Glu Thr Asp Gln Asn Glu Ser Gln Ser Pro Gln Glu Pro 3195 32003205 gag gaa ggc ccc agt gaa gat gac aag gca gaa ggg gaa gag gaa 10707Glu Glu Gly Pro Ser Glu Asp Asp Lys Ala Glu Gly Glu Glu Glu 3210 32153220 atg gac aca gga gct gat gac caa gat gga gat gct gct cag cat 10752Met Asp Thr Gly Ala Asp Asp Gln Asp Gly Asp Ala Ala Gln His 3225 32303235 cct gaa gaa cac tct gag gag cag cag cag tct gtg gag gaa aaa 10797Pro Glu Glu His Ser Glu Glu Gln Gln Gln Ser Val Glu Glu Lys 3240 32453250 gac aag gaa gcc gat gaa gaa ggt gga gag aat ggc cct gct gac 10842Asp Lys Glu Ala Asp Glu Glu Gly Gly Glu Asn Gly Pro Ala Asp 3255 32603265 caa ggt ttc cag ccc cag gag gaa gaa gaa cgg gag gac tct gat 10887Gln Gly Phe Gln Pro Gln Glu Glu Glu Glu Arg Glu Asp Ser Asp 3270 32753280 aca gag gag cag gtg cca gag gct ttg gag agg aag gag cat gcc 10932Thr Glu Glu Gln Val Pro Glu Ala Leu Glu Arg Lys Glu His Ala 3285 32903295 tcc tgt ggg cag act ggt gtg gag aac atg cag aac aca cag gcc 10977Ser Cys Gly Gln Thr Gly Val Glu Asn Met Gln Asn Thr Gln Ala 3300 33053310 atg gag ctg gct ggg gcc gca cct gag aag gag cag ggg aaa gag 11022Met Glu Leu Ala Gly Ala Ala Pro Glu Lys Glu Gln Gly Lys Glu 3315 33203325 gaa cac gga agt gga gct gca gat gca aac cag gca gaa ggc cat 11067Glu His Gly Ser Gly Ala Ala Asp Ala Asn Gln Ala Glu Gly His 3330 33353340 gaa tcg aat ttc att gcc cag ttg gcc tcc cag aag cac acc agg 11112Glu Ser Asn Phe Ile Ala Gln Leu Ala Ser Gln Lys His Thr Arg 3345 33503355 aaa aac aca cag agt ttt aag agg aaa cct ggg cag gct gac aat 11157Lys Asn Thr Gln Ser Phe Lys Arg Lys Pro Gly Gln Ala Asp Asn 3360 33653370 gaa cgt tcc atg ggt gat cac aat gag cgt gtg cac aag agg ctg 11202Glu Arg Ser Met Gly Asp His Asn Glu Arg Val His Lys Arg Leu 3375 33803385 agg act gtg gat acg gac agc cat gcc gag cag ggg cca gct cag 11247Arg Thr Val Asp Thr Asp Ser His Ala Glu Gln Gly Pro Ala Gln 3390 33953400 cag ccc cag gcc cag gtg gag gat gca gat gca ttc gag cac att 11292Gln Pro Gln Ala Gln Val Glu Asp Ala Asp Ala Phe Glu His Ile 3405 34103415 aaa caa ggc agt gac gca tac gat gca cag acc tat gat gtg gcc 11337Lys Gln Gly Ser Asp Ala Tyr Asp Ala Gln Thr Tyr Asp Val Ala 3420 34253430 agc aaa gaa cag caa cag tct gca aaa gac tct ggc aaa gat cag 11382Ser Lys Glu Gln Gln Gln Ser Ala Lys Asp Ser Gly Lys Asp Gln 3435 34403445 gaa gag gag gag ata gag gac acc ctt atg gac aca gag gag cag 11427Glu Glu Glu Glu Ile Glu Asp Thr Leu Met Asp Thr Glu Glu Gln 3450 34553460 gag gag ttc aaa gca gca gac gtg gag cag ctg aag cca gag gaa 11472Glu Glu Phe Lys Ala Ala Asp Val Glu Gln Leu Lys Pro Glu Glu 3465 34703475 atc aag tcg ggc acc aca gca ccc ttg ggc ttt gat gag atg gaa 11517Ile Lys Ser Gly Thr Thr Ala Pro Leu Gly Phe Asp Glu Met Glu 3480 34853490 gtg gag atc caa act gtt aaa aca gag gaa gac caa gac ccc aga 11562Val Glu Ile Gln Thr Val Lys Thr Glu Glu Asp Gln Asp Pro Arg 3495 35003505 aca gac aaa gcc cat aag gag aca gaa aat gag aaa cca gaa aga 11607Thr Asp Lys Ala His Lys Glu Thr Glu Asn Glu Lys Pro Glu Arg 3510 35153520 agc cga gag tct acc att cat aca gct cat caa ttc ctc atg gac 11652Ser Arg Glu Ser Thr Ile His Thr Ala His Gln Phe Leu Met Asp 3525 35303535 acg atc ttc cag ccc ttt tta aaa gat gtc aat gag cta aga cag 11697Thr Ile Phe Gln Pro Phe Leu Lys Asp Val Asn Glu Leu Arg Gln 3540 35453550 gag ctg gag aga cag ctg gaa atg tgg cag cca cgt gaa tct gga 11742Glu Leu Glu Arg Gln Leu Glu Met Trp Gln Pro Arg Glu Ser Gly 3555 35603565 aac cca gag gag gag aag gtt gca gct gag atg tgg cag agt tac 11787Asn Pro Glu Glu Glu Lys Val Ala Ala Glu Met Trp Gln Ser Tyr 3570 35753580 ctg atc tta aca gcg cct ctt tca caa cgg tta tgt gaa gag ctt 11832Leu Ile Leu Thr Ala Pro Leu Ser Gln Arg Leu Cys Glu Glu Leu 3585 35903595 cgt ctc ata tta gag cct acc cag gca gcc aag ctg aaa gga gac 11877Arg Leu Ile Leu Glu Pro Thr Gln Ala Ala Lys Leu Lys Gly Asp 3600 36053610 tat cga act ggg aaa cga cta aac ata cgg aaa gtc att cca tac 11922Tyr Arg Thr Gly Lys Arg Leu Asn Ile Arg Lys Val Ile Pro Tyr 3615 36203625 att gct agt caa ttt cgg aaa gac aag att tgg ctt cga agg acc 11967Ile Ala Ser Gln Phe Arg Lys Asp Lys Ile Trp Leu Arg Arg Thr 3630 36353640 aag ccc agt aaa cgc cag tat cag att tgt ttg gct atc gat gac 12012Lys Pro Ser Lys Arg Gln Tyr Gln Ile Cys Leu Ala Ile Asp Asp 3645 36503655 tct tct agt atg gta gac aat cat acc aag cag ctt gca ttt gaa 12057Ser Ser Ser Met Val Asp Asn His Thr Lys Gln Leu Ala Phe Glu 3660 36653670 tct ttg gct gtg att gga aat gct cta acc ctc ctg gaa gtg ggt 12102Ser Leu Ala Val Ile Gly Asn Ala Leu Thr Leu Leu Glu Val Gly 3675 36803685 cag att gca gtg tgt agt ttt gga gaa tct gta aag ctg tta cac 12147Gln Ile Ala Val Cys Ser Phe Gly Glu Ser Val Lys Leu Leu His 3690 36953700 cca ttt cat gag cag ttc agt gat tac tct ggg tcc cag att cta 12192Pro Phe His Glu Gln Phe Ser Asp Tyr Ser Gly Ser Gln Ile Leu 3705 37103715 cgt ctc tgc aaa ttc caa caa aag aaa acc aag att gct cag ttt 12237Arg Leu Cys Lys Phe Gln Gln Lys Lys Thr Lys Ile Ala Gln Phe 3720 37253730 cta gag tct gtt gcc aac atg ttt gca gct gct cag cag ctc tcg 12282Leu Glu Ser Val Ala Asn Met Phe Ala Ala Ala Gln Gln Leu Ser 3735 37403745 cag aac atc agt tca gaa act gca caa ctc ctc ctg gta gtc tct 12327Gln Asn Ile Ser Ser Glu Thr Ala Gln Leu Leu Leu Val Val Ser 3750 37553760 gat ggg cga ggc ctt ttc ctt gag ggc aaa gaa aga gtc ctg gca 12372Asp Gly Arg Gly Leu Phe Leu Glu Gly Lys Glu Arg Val Leu Ala 3765 37703775 gca gtt cag gct gcc cgg aat gca aat atc ttt gtc atc ttt gtt 12417Ala Val Gln Ala Ala Arg Asn Ala Asn Ile Phe Val Ile Phe Val 3780 37853790 gta ttg gac aat ccc agt tca cgg gat tct atc ttg gac att aaa 12462Val Leu Asp Asn Pro Ser Ser Arg Asp Ser Ile Leu Asp Ile Lys 3795 38003805 gta ccg ata ttt aaa gga cct gga gag atg cct gaa atc cga tcc 12507Val Pro Ile Phe Lys Gly Pro Gly Glu Met Pro Glu Ile Arg Ser 3810 38153820 tac atg gaa gag ttc cca ttc cca tac tat atc att ctt cga gat 12552Tyr Met Glu Glu Phe Pro Phe Pro Tyr Tyr Ile Ile Leu Arg Asp 3825 38303835 gta aac gca ctt cct gag aca ctc agc gat gcc ctc aga cag tgg 12597Val Asn Ala Leu Pro Glu Thr Leu Ser Asp Ala Leu Arg Gln Trp 3840 38453850 ttt gag ttg gtg aca gcc tct gac cac cca tag aacagaaaga 12640 PheGlu Leu Val Thr Ala Ser Asp His Pro 3855 3860 agagtccaaa gtgagacttaactgtggtca gaaggtcaca ttgcttaccc aggtgctccc 12700 ttttggacaa ctacaaaaaattttattgta atatttttat tttacaacgt gatcttacag 12760 cctacagaat gctctctggctcccggcttt gcctgggctg aggtttttat accaaacctg 12820 gaagcagcag caggtgcctgaactcgtaac tagagaagag ttatccttct tccctgcctt 12880 ggaagccctg gcctgggaggaggtcatacc ccaccgttgg agcccagctg cctgttttct 12940 tttgcagggg atctgggcacctgtgccttg aggagatgct gccaggagca tgggactctg 13000 acagtccttt gtataaaggactaaagggag ctgccctttt gaccctgttc taagctctgc 13060 cttgccaagc ccatagtgtgtgcccaaaag ctgtcaagtg gccaagacag ctcgtttctg 13120 gagagtatga gggtgtgttttcttattgtg aaaggaacta ccttctctta gagggtagga 13180 agaatgtggt gtgtgtgtgttctcataaag caactggaca ttataggtgc ccaggtcatc 13240 tataaaaacg atccttgggctgtgtaaaaa tgaagtggct tttcagtatc ctctttcaca 13300 cttgctgctt cgggagactatgcaatgatg ggaaggtgat tgccccttta tttcattcag 13360 tgccatggtc cctgttgttgtagtaattta tttgtttagt tcattttttt ttttcttaac 13420 agtcaagggg aagagtgattcctcacactg ctttcaagct ggactgagcc agtctcattc 13480 tgggaaagaa acgctgtgtccagaactcag cagctccatc tattttttcc agtcgaaaga 13540 aactgatctt taggcagtttttacttggcc agaaagcagt gctgaatact tgaaactgtg 13600 tgctctgttc tacttaatgttctgtcagaa tgttcttttg taggcagtat gtcatgatgt 13660 aatcatctat ctccttgtctgtttccaagt tacactgtga agtctgcgac ccttttgagg 13720 tggtcatcaa agacacagattccttgttta accaagtgtc ccaaagcatg tacctgaagt 13780 tatatcattt tttattctaaaaagctatgc agcttatatt ctgaaaacta ttaaaacata 13840 taccactgtt gttgatgtaatttgtgactc ttcttaatgg aagatgacag gattgtaaaa 13900 ggtatgctag gggactgatcttctctgctg gatcagtcag tcagctgtta ctagttgatg 13960 ctgtgctaac atgatcccctcctacttcca tgttgctctt actacaaagg ttatcatttg 14020 catttatgtc catggtaggctgagctataa tatgctggct ttgcagcaga atgaaaagga 14080 tgagttggtg tagccttataa 14101 7 3863 PRT Homo sapiens 7 Met Asn Ala Gln Arg Leu Leu Arg AlaThr Lys Leu Lys Lys Pro Ile 1 5 10 15 Leu Leu Glu Gly Ser Pro Gly ValGly Lys Thr Ser Leu Val Gly Ala 20 25 30 Leu Ala Lys Ala Ser Gly Asn ThrLeu Val Arg Ile Asn Leu Ser Glu 35 40 45 Gln Thr Asp Ile Thr Asp Leu PheGly Ala Asp Leu Pro Val Glu Gly 50 55 60 Gly Lys Gly Gly Glu Phe Ala TrpArg Asp Gly Pro Leu Leu Ala Ala 65 70 75 80 Leu Lys Ala Gly His Trp ValVal Leu Asp Glu Leu Asn Leu Ala Ser 85 90 95 Gln Ser Val Leu Glu Gly LeuAsn Ala Cys Phe Asp His Arg Gly Glu 100 105 110 Ile Tyr Val Pro Glu LeuGly Met Ser Phe Gln Val Gln His Glu Lys 115 120 125 Thr Lys Ile Phe GlyCys Gln Asn Pro Phe Arg Gln Gly Gly Gly Arg 130 135 140 Lys Gly Leu ProArg Ser Phe Leu Asn Arg Phe Thr Gln Val Phe Val 145 150 155 160 Asp ProLeu Thr Val Ile Asp Met Glu Phe Ile Ala Ser Thr Leu Phe 165 170 175 ProAla Ile Glu Lys Asn Ile Val Lys Lys Met Val Ala Phe Asn Asn 180 185 190Gln Ile Asp His Glu Val Thr Val Glu Lys Lys Trp Gly Gln Lys Gly 195 200205 Gly Pro Trp Glu Phe Asn Leu Arg Asp Leu Phe Arg Trp Cys Gln Leu 210215 220 Met Leu Val Asp Gln Ser Pro Gly Cys Tyr Asp Pro Gly Gln His Val225 230 235 240 Phe Leu Val Tyr Gly Glu Arg Met Arg Thr Glu Glu Asp LysLys Lys 245 250 255 Val Ile Ala Val Phe Lys Asp Val Phe Gly Ser Asn SerAsn Pro Tyr 260 265 270 Met Gly Thr Arg Leu Phe Arg Ile Thr Pro Tyr AspVal Gln Leu Gly 275 280 285 Tyr Ser Val Leu Ser Arg Gly Ser Cys Val ProHis Pro Ser Arg His 290 295 300 Pro Leu Leu Leu Leu His Gln Ser Phe GlnPro Leu Glu Ser Ile Met 305 310 315 320 Lys Cys Val Gln Met Ser Trp MetVal Ile Leu Val Gly Pro Ala Ser 325 330 335 Val Gly Lys Thr Ser Leu ValGln Leu Leu Ala His Leu Thr Gly His 340 345 350 Thr Leu Lys Ile Met AlaMet Asn Ser Ala Met Asp Thr Thr Glu Leu 355 360 365 Leu Gly Gly Phe GluGln Val Asp Leu Ile Arg Pro Trp Arg Arg Leu 370 375 380 Leu Glu Lys ValGlu Gly Thr Val Arg Ala Leu Leu Arg Asp Ser Leu 385 390 395 400 Leu IleSer Ala Asp Asp Ala Glu Val Val Leu Arg Ala Trp Ser His 405 410 415 PheLeu Leu Thr Tyr Lys Pro Lys Cys Leu Gly Glu Gly Gly Lys Ala 420 425 430Ile Thr Met Glu Ile Val Asn Lys Leu Glu Ala Val Leu Leu Leu Met 435 440445 Gln Arg Leu Asn Asn Lys Ile Asn Ser Tyr Cys Lys Ala Glu Phe Ala 450455 460 Lys Leu Val Glu Glu Phe Arg Ser Phe Gly Val Lys Leu Thr Gln Leu465 470 475 480 Ala Ser Gly His Ser His Gly Thr Phe Glu Trp Val Asp SerMet Leu 485 490 495 Val Gln Ala Leu Lys Ser Gly Asp Trp Leu Leu Met AspAsn Val Asn 500 505 510 Phe Cys Asn Pro Ser Val Leu Asp Arg Leu Asn AlaLeu Leu Glu Pro 515 520 525 Gly Gly Val Leu Thr Ile Ser Glu Arg Gly MetIle Asp Gly Ser Thr 530 535 540 Pro Thr Ile Thr Pro Asn Pro Asn Phe ArgLeu Phe Leu Ser Met Asp 545 550 555 560 Pro Val His Gly Asp Ile Ser ArgAla Met Arg Asn Arg Gly Leu Glu 565 570 575 Ile Tyr Ile Ser Gly Glu GlyAsp Ala Ser Thr Pro Asp Asn Leu Asp 580 585 590 Leu Lys Val Leu Leu HisSer Leu Gly Leu Val Gly Asn Ser Val Cys 595 600 605 Asp Ile Leu Leu AlaLeu His Thr Glu Thr Arg Ser Thr Val Val Gly 610 615 620 Ser Pro Thr SerSer Val Ser Thr Leu Ile Gln Thr Ala Ile Leu Ile 625 630 635 640 Val GlnTyr Leu Gln Arg Gly Leu Ser Leu Asp Arg Ala Phe Ser Glu 645 650 655 AlaCys Trp Glu Val Tyr Val Cys Ser Gln His Ser Pro Ala Asn Arg 660 665 670Lys Leu Val Gln Ala Leu Leu Glu Lys His Val Ser Ser Leu Arg Ala 675 680685 His Glu Thr Trp Gly Asp Ser Ile Leu Gly Met Gly Leu Trp Pro Asp 690695 700 Ser Val Pro Ser Ala Leu Phe Ala Thr Glu Asp Ser His Leu Ser Thr705 710 715 720 Val Arg Arg Asp Gly Gln Ile Leu Val Tyr Cys Leu Asn ArgMet Ser 725 730 735 Met Lys Thr Ser Ser Trp Thr Arg Ser Gln Pro Phe ThrLeu Gln Asp 740 745 750 Leu Glu Lys Ile Met Gln Ser Pro Ser Pro Glu AsnLeu Lys Phe Asn 755 760 765 Ala Val Glu Val Asn Thr Tyr Trp Ile Asp GluPro Asp Val Leu Val 770 775 780 Met Ala Val Lys Leu Leu Ile Glu Arg AlaThr Asn Gln Asp Trp Met 785 790 795 800 Leu Arg Val Lys Trp Leu Tyr HisLeu Ala Lys Asn Ile Pro Gln Gly 805 810 815 Leu Glu Ser Ile Gln Ile HisLeu Glu Ala Ser Ala Ala Ser Leu Arg 820 825 830 Asn Phe Tyr Ser His SerLeu Ser Gly Ala Val Ser Asn Val Phe Lys 835 840 845 Ile Leu Gln Pro AsnThr Thr Asp Glu Phe Val Ile Pro Leu Asp Pro 850 855 860 Arg Trp Asn MetGln Ala Leu Asp Met Ile Arg Asn Leu Met Asp Phe 865 870 875 880 Asp ProGln Thr Asp Gln Pro Asp Gln Leu Phe Ala Leu Leu Glu Ser 885 890 895 AlaAla Asn Lys Thr Ile Ile Tyr Leu Asp Arg Glu Lys Arg Val Phe 900 905 910Thr Glu Ala Asn Leu Val Ser Val Gly Ser Lys Lys Leu Arg Glu Ser 915 920925 Val Leu Arg Met Ser Phe Glu Phe His Gln Asp Pro Glu Ser Tyr His 930935 940 Thr Leu Pro His Glu Ile Val Val Asn Leu Ala Ala Phe Phe Glu Leu945 950 955 960 Cys Asp Ala Leu Val Leu Leu Trp Val Gln Ser Ser Gln GlyMet Val 965 970 975 Ser Asp Ala Ser Ala Asn Glu Ile Leu Gly Ser Leu ArgTrp Arg Asp 980 985 990 Arg Phe Trp Thr Val Ala Asp Thr Val Lys Val AspAla Pro Gly Leu 995 1000 1005 Ala Leu Leu Ala Leu His Trp His Trp ValLeu Lys His Leu Val 1010 1015 1020 His Gln Ile Pro Arg Leu Leu Met AsnTyr Glu Asp Lys Tyr Tyr 1025 1030 1035 Lys Glu Val Gln Thr Val Ser GluHis Ile Gln Asn Cys Leu Gly 1040 1045 1050 Ser Gln Thr Gly Gly Phe AlaGly Ile Lys Lys Leu Gln Lys Phe 1055 1060 1065 Leu Gly Arg Pro Phe ProPhe Lys Asp Lys Leu Val Val Glu Cys 1070 1075 1080 Phe Ser Gln Leu LysVal Leu Asn Lys Val Leu Ala Ile Arg Glu 1085 1090 1095 Gln Met Ser AlaLeu Gly Glu Ser Gly Trp Gln Glu Asp Ile Asn 1100 1105 1110 Arg Leu GlnVal Val Ala Ser Gln Trp Thr Leu Lys Lys Ser Leu 1115 1120 1125 Leu GlnAla Trp Gly Leu Ile Leu Arg Ala Asn Ile Leu Glu Asp 1130 1135 1140 ValSer Leu Asp Glu Leu Lys Asn Phe Val His Ala Gln Cys Leu 1145 1150 1155Glu Leu Lys Ala Lys Gly Leu Ser Leu Gly Phe Leu Glu Lys Lys 1160 11651170 His Asp Glu Ala Ser Ser Leu Ser His Pro Asp Leu Thr Ser Val 11751180 1185 Ile His Leu Thr Arg Ser Val Gln Leu Trp Pro Ala Met Glu Tyr1190 1195 1200 Leu Ala Met Leu Trp Arg Tyr Lys Val Thr Ala Asp Phe MetAla 1205 1210 1215 Gln Ala Cys Leu Arg Arg Cys Ser Lys Asn Gln Gln ProGln Ile 1220 1225 1230 Asn Glu Glu Ile Ser His Leu Ile Ser Phe Cys LeuTyr His Thr 1235 1240 1245 Pro Val Thr Pro Gln Glu Leu Arg Asp Leu TrpSer Leu Leu His 1250 1255 1260 His Gln Lys Val Ser Pro Glu Glu Ile ThrSer Leu Trp Ser Glu 1265 1270 1275 Leu Phe Asn Ser Met Phe Met Ser PheTrp Ser Ser Thr Val Thr 1280 1285 1290 Thr Asn Pro Glu Tyr Trp Leu MetTrp Asn Pro Leu Pro Gly Met 1295 1300 1305 Gln Gln Arg Glu Ala Pro LysSer Val Leu Asp Ser Thr Leu Lys 1310 1315 1320 Gly Pro Gly Asn Leu AsnArg Pro Ile Phe Ser Lys Cys Cys Phe 1325 1330 1335 Glu Val Leu Thr SerSer Trp Arg Ala Ser Pro Trp Asp Val Ser 1340 1345 1350 Gly Leu Pro IleLeu Ser Ser Ser His Val Thr Leu Gly Glu Trp 1355 1360 1365 Val Glu ArgThr Gln Gln Leu Gln Asp Ile Ser Ser Met Leu Trp 1370 1375 1380 Thr AsnMet Ala Ile Ser Ser Val Ala Glu Phe Arg Arg Thr Asp 1385 1390 1395 SerGln Leu Gln Gly Gln Val Leu Phe Arg His Leu Ala Gly Leu 1400 1405 1410Ala Glu Leu Leu Pro Glu Ser Arg Arg Gln Glu Tyr Met Gln Asn 1415 14201425 Cys Glu Gln Leu Leu Leu Gly Ser Ser Gln Ala Phe Gln His Val 14301435 1440 Gly Gln Thr Leu Gly Asp Met Ala Gly Gln Glu Val Leu Pro Lys1445 1450 1455 Glu Leu Leu Cys Gln Leu Leu Thr Ser Leu His His Phe ValGly 1460 1465 1470 Glu Gly Glu Ser Lys Arg Ser Leu Pro Glu Pro Ala GlnArg Gly 1475 1480 1485 Ser Leu Trp Val Ser Leu Gly Leu Leu Gln Ile GlnThr Trp Leu 1490 1495 1500 Pro Gln Ala Arg Phe Asp Pro Ala Val Lys ArgGlu Tyr Lys Leu 1505 1510 1515 Asn Tyr Val Lys Glu Glu Leu His Gln LeuGln Cys Glu Trp Lys 1520 1525 1530 Thr Arg Asn Leu Ser Ser Gln Leu GlnThr Gly Arg Asp Leu Glu 1535 1540 1545 Asp Glu Val Val Val Ser Tyr SerHis Pro His Val Arg Leu Leu 1550 1555 1560 Arg Gln Arg Met Asp Arg LeuAsp Asn Leu Thr Cys His Leu Leu 1565 1570 1575 Lys Lys Gln Ala Phe ArgPro Gln Leu Pro Ala Tyr Glu Ser Leu 1580 1585 1590 Val Gln Glu Ile HisHis Tyr Val Thr Ser Ile Ala Lys Ala Pro 1595 1600 1605 Ala Val Gln AspLeu Leu Thr Arg Leu Leu Gln Ala Leu His Ile 1610 1615 1620 Asp Gly ProArg Ser Ala Gln Val Ala Gln Ser Leu Leu Lys Glu 1625 1630 1635 Glu AlaSer Trp Gln Gln Ser His His Gln Phe Arg Lys Arg Leu 1640 1645 1650 SerGlu Glu Tyr Thr Phe Tyr Pro Asp Ala Val Ser Pro Leu Gln 1655 1660 1665Ala Ser Ile Leu Gln Leu Gln His Gly Met Arg Leu Val Ala Ser 1670 16751680 Glu Leu His Thr Ser Leu Tyr Ser Ser Met Val Gly Ala Asp Arg 16851690 1695 Leu Gly Thr Leu Ala Thr Ala Leu Leu Ala Phe Pro Ser Val Gly1700 1705 1710 Pro Thr Phe Pro Thr Tyr Tyr Ala His Ala Asp Thr Leu CysSer 1715 1720 1725 Val Lys Ser Glu Glu Val Leu Arg Gly Leu Gly Lys LeuIle Leu 1730 1735 1740 Lys Arg Ser Gly Gly Lys Glu Leu Glu Gly Lys GlyGln Lys Ala 1745 1750 1755 Cys Pro Thr Arg Glu Gln Leu Leu Met Asn AlaLeu Leu Tyr Leu 1760 1765 1770 Arg Ser His Val Leu Cys Lys Gly Glu LeuAsp Gln Arg Ala Leu 1775 1780 1785 Gln Leu Phe Arg His Val Cys Gln GluIle Ile Ser Glu Trp Asp 1790 1795 1800 Glu Gln Glu Arg Ile Ala Gln GluLys Ala Glu Gln Glu Ser Gly 1805 1810 1815 Leu Tyr Arg Tyr Arg Ser ArgAsn Ser Arg Thr Ala Leu Ser Glu 1820 1825 1830 Glu Glu Glu Glu Glu ArgGlu Phe Arg Lys Gln Phe Pro Leu His 1835 1840 1845 Glu Lys Asp Phe AlaAsp Ile Leu Val Gln Pro Thr Leu Glu Glu 1850 1855 1860 Asn Lys Gly ThrSer Asp Gly Gln Glu Glu Glu Ala Gly Thr Asn 1865 1870 1875 Pro Ala LeuLeu Ser Gln Asn Ser Met Gln Ala Val Met Leu Ile 1880 1885 1890 His GlnGln Leu Cys Leu Asn Phe Ala Arg Ser Leu Trp Tyr Gln 1895 1900 1905 GlnThr Leu Pro Pro His Glu Ala Lys His Tyr Leu Ser Leu Phe 1910 1915 1920Leu Ser Cys Tyr Gln Thr Gly Ala Ser Leu Val Thr His Phe Tyr 1925 19301935 Pro Leu Met Gly Val Glu Leu Asn Asp Arg Leu Leu Gly Ser Gln 19401945 1950 Leu Leu Ala Cys Thr Leu Ser His Asn Thr Leu Phe Gly Glu Ala1955 1960 1965 Pro Ser Asp Leu Met Val Lys Pro Asp Gly Pro Tyr Asp PheTyr 1970 1975 1980 Gln His Pro Asn Val Pro Glu Ala Arg Gln Cys Gln ProVal Leu 1985 1990 1995 Gln Gly Phe Ser Glu Ala Val Ser His Leu Leu GlnAsp Trp Pro 2000 2005 2010 Glu His Pro Ala Leu Glu Gln Leu Leu Val ValMet Asp Arg Ile 2015 2020 2025 Arg Ser Phe Pro Leu Ser Ser Pro Ile SerLys Phe Leu Asn Gly 2030 2035 2040 Leu Glu Ile Leu Leu Ala Lys Ala GlnAsp Trp Glu Glu Asn Ala 2045 2050 2055 Ser Arg Ala Leu Ser Leu Arg LysHis Leu Asp Leu Ile Ser Gln 2060 2065 2070 Met Ile Ile Arg Trp Arg LysLeu Glu Leu Asn Cys Trp Ser Met 2075 2080 2085 Ser Leu Asp Asn Thr MetLys Arg His Thr Glu Lys Ser Thr Lys 2090 2095 2100 His Trp Phe Ser IleTyr Gln Met Leu Glu Lys His Met Gln Glu 2105 2110 2115 Gln Thr Glu GluGln Glu Asp Asp Lys Gln Met Thr Leu Met Leu 2120 2125 2130 Leu Val SerThr Leu Gln Ala Phe Ile Glu Gly Ser Ser Leu Gly 2135 2140 2145 Glu PheHis Val Arg Leu Gln Met Leu Leu Val Phe His Cys His 2150 2155 2160 ValLeu Leu Met Pro Gln Val Glu Gly Lys Asp Ser Leu Cys Ser 2165 2170 2175Val Leu Trp Asn Leu Tyr His Tyr Tyr Lys Gln Phe Phe Asp Arg 2180 21852190 Val Gln Ala Lys Ile Val Glu Leu Arg Ser Pro Leu Glu Lys Glu 21952200 2205 Leu Lys Glu Phe Val Lys Ile Ser Lys Trp Asn Asp Val Ser Phe2210 2215 2220 Trp Ser Ile Lys Gln Ser Val Glu Lys Thr His Arg Thr LeuPhe 2225 2230 2235 Lys Phe Met Lys Lys Phe Glu Ala Val Leu Ser Glu ProCys Arg 2240 2245 2250 Ser Ser Leu Val Glu Ser Asp Lys Glu Glu Gln ProAsp Phe Leu 2255 2260 2265 Pro Arg Pro Thr Asp Gly Ala Ala Ser Glu LeuSer Ser Ile Gln 2270 2275 2280 Asn Leu Asn Arg Ala Leu Arg Glu Thr LeuLeu Ala Gln Pro Ala 2285 2290 2295 Ala Gly Gln Ala Thr Ile Pro Glu TrpCys Gln Gly Ala Ala Pro 2300 2305 2310 Ser Gly Leu Glu Gly Glu Leu LeuArg Arg Leu Pro Lys Leu Arg 2315 2320 2325 Lys Arg Met Arg Lys Met CysLeu Thr Phe Met Lys Glu Ser Pro 2330 2335 2340 Leu Pro Arg Leu Val GluGly Leu Asp Gln Phe Thr Gly Glu Val 2345 2350 2355 Ile Ser Ser Val SerGlu Leu Gln Ser Leu Lys Val Glu Pro Ser 2360 2365 2370 Ala Glu Lys GluLys Gln Arg Ser Glu Ala Lys His Ile Leu Met 2375 2380 2385 Gln Lys GlnArg Ala Leu Ser Asp Leu Phe Lys His Leu Ala Lys 2390 2395 2400 Ile GlyLeu Ser Tyr Arg Lys Gly Leu Ala Trp Ala Arg Ser Lys 2405 2410 2415 AsnPro Gln Glu Met Leu His Leu His Pro Leu Asp Leu Gln Ser 2420 2425 2430Ala Leu Ser Ile Val Ser Ser Thr Gln Glu Ala Asp Ser Arg Leu 2435 24402445 Leu Thr Glu Ile Ser Ser Ser Trp Asp Gly Cys Gln Lys Tyr Phe 24502455 2460 Tyr Arg Ser Leu Ala Arg His Ala Arg Leu Asn Ala Ala Leu Ala2465 2470 2475 Thr Pro Ala Lys Glu Met Gly Met Gly Asn Val Glu Arg CysArg 2480 2485 2490 Gly Phe Ser Ala His Leu Met Lys Met Leu Val Arg GlnArg Arg 2495 2500 2505 Ser Leu Thr Thr Leu Ser Glu Gln Trp Ile Ile LeuArg Asn Leu 2510 2515 2520 Leu Ser Cys Val Gln Glu Ile His Ser Arg LeuMet Gly Pro Gln 2525 2530 2535 Ala Tyr Pro Val Ala Phe Pro Pro Gln AspGly Val Gln Gln Trp 2540 2545 2550 Thr Glu Arg Leu Gln His Leu Ala MetGln Cys Gln Ile Leu Leu 2555 2560 2565 Glu Gln Leu Ser Trp Leu Leu GlnCys Cys Pro Ser Val Gly Pro 2570 2575 2580 Ala Pro Gly His Gly Asn ValGln Val Leu Gly Gln Pro Pro Gly 2585 2590 2595 Pro Cys Leu Glu Gly ProGlu Leu Ser Lys Gly Gln Leu Cys Gly 2600 2605 2610 Val Val Leu Asp LeuIle Pro Ser Asn Leu Ser Tyr Pro Ser Pro 2615 2620 2625 Ile Pro Gly SerGln Leu Pro Ser Gly Cys Arg Met Arg Lys Gln 2630 2635 2640 Asp His LeuTrp Gln Gln Ser Thr Thr Arg Leu Thr Glu Met Leu 2645 2650 2655 Lys ThrIle Lys Thr Val Lys Ala Asp Val Asp Lys Ile Arg Gln 2660 2665 2670 GlnSer Cys Glu Thr Leu Phe His Ser Trp Lys Asp Phe Glu Val 2675 2680 2685Cys Ser Ser Ala Leu Ser Cys Leu Ser Gln Val Ser Val His Leu 2690 26952700 Gln Gly Leu Glu Ser Leu Phe Ile Leu Pro Gly Met Glu Val Glu 27052710 2715 Gln Arg Asp Ser Gln Met Ala Leu Val Glu Ser Leu Glu Tyr Val2720 2725 2730 Arg Gly Glu Ile Ser Lys Ala Met Ala Asp Phe Thr Thr TrpLys 2735 2740 2745 Thr His Leu Leu Thr Ser Asp Ser Gln Gly Gly Asn GlnMet Leu 2750 2755 2760 Asp Glu Gly Phe Val Glu Asp Phe Ser Glu Gln MetGlu Ile Ala 2765 2770 2775 Ile Arg Ala Ile Leu Cys Ala Ile Gln Asn LeuGlu Glu Arg Lys 2780 2785 2790 Asn Glu Lys Ala Glu Glu Asn Thr Asp GlnAla Ser Pro Gln Glu 2795 2800 2805 Asp Tyr Ala Gly Phe Glu Arg Leu GlnSer Gly His Leu Thr Lys 2810 2815 2820 Leu Leu Glu Asp Asp Phe Trp AlaAsp Val Ser Thr Leu His Val 2825 2830 2835 Gln Lys Ile Ile Ser Ala IleSer Glu Leu Leu Glu Arg Leu Lys 2840 2845 2850 Ser Tyr Gly Glu Asp GlyThr Ala Ala Lys His Leu Phe Phe Ser 2855 2860 2865 Gln Ser Cys Ser LeuLeu Val Arg Leu Val Pro Val Leu Ser Ser 2870 2875 2880 Tyr Ser Asp LeuVal Leu Phe Phe Leu Thr Met Ser Leu Ala Thr 2885 2890 2895 His Arg SerThr Ala Lys Leu Leu Ser Val Leu Ala Gln Val Phe 2900 2905 2910 Thr GluLeu Ala Gln Lys Gly Phe Cys Leu Pro Lys Glu Phe Met 2915 2920 2925 GluAsp Ser Ala Gly Glu Gly Ala Thr Glu Phe His Asp Tyr Glu 2930 2935 2940Gly Gly Gly Ile Gly Glu Gly Glu Gly Met Lys Asp Val Ser Asp 2945 29502955 Gln Ile Gly Asn Glu Glu Gln Val Glu Asp Thr Phe Gln Lys Gly 29602965 2970 Gln Glu Lys Asp Lys Glu Asp Pro Asp Ser Lys Ser Asp Ile Lys2975 2980 2985 Gly Glu Asp Asn Ala Ile Glu Met Ser Glu Asp Phe Asp GlyLys 2990 2995 3000 Met His Asp Gly Glu Leu Glu Glu Gln Glu Glu Asp AspGlu Lys 3005 3010 3015 Ser Asp Ser Glu Gly Gly Asp Leu Asp Lys His MetGly Asp Leu 3020 3025 3030 Asn Gly Glu Glu Ala Asp Lys Leu Asp Glu ArgLeu Trp Gly Asp 3035 3040 3045 Asp Asp Glu Glu Glu Asp Glu Glu Glu GluAsp Asn Lys Thr Glu 3050 3055 3060 Glu Thr Gly Pro Gly Met Asp Glu GluAsp Ser Glu Leu Val Ala 3065 3070 3075 Lys Asp Asp Asn Leu Asp Ser GlyAsn Ser Asn Lys Asp Lys Ser 3080 3085 3090 Gln Gln Asp Lys Lys Glu GluLys Glu Glu Ala Glu Ala Asp Asp 3095 3100 3105 Gly Gly Gln Gly Glu AspLys Ile Asn Glu Gln Ile Asp Glu Arg 3110 3115 3120 Asp Tyr Asp Glu AsnGlu Val Asp Pro Tyr His Gly Asn Gln Glu 3125 3130 3135 Lys Val Pro GluPro Glu Ala Leu Asp Leu Pro Asp Asp Leu Asn 3140 3145 3150 Leu Asp SerGlu Asp Lys Asn Gly Gly Glu Asp Thr Asp Asn Glu 3155 3160 3165 Glu GlyGlu Glu Glu Asn Pro Leu Glu Ile Lys Glu Lys Pro Glu 3170 3175 3180 GluAla Gly His Glu Ala Glu Glu Arg Gly Glu Thr Glu Thr Asp 3185 3190 3195Gln Asn Glu Ser Gln Ser Pro Gln Glu Pro Glu Glu Gly Pro Ser 3200 32053210 Glu Asp Asp Lys Ala Glu Gly Glu Glu Glu Met Asp Thr Gly Ala 32153220 3225 Asp Asp Gln Asp Gly Asp Ala Ala Gln His Pro Glu Glu His Ser3230 3235 3240 Glu Glu Gln Gln Gln Ser Val Glu Glu Lys Asp Lys Glu AlaAsp 3245 3250 3255 Glu Glu Gly Gly Glu Asn Gly Pro Ala Asp Gln Gly PheGln Pro 3260 3265 3270 Gln Glu Glu Glu Glu Arg Glu Asp Ser Asp Thr GluGlu Gln Val 3275 3280 3285 Pro Glu Ala Leu Glu Arg Lys Glu His Ala SerCys Gly Gln Thr 3290 3295 3300 Gly Val Glu Asn Met Gln Asn Thr Gln AlaMet Glu Leu Ala Gly 3305 3310 3315 Ala Ala Pro Glu Lys Glu Gln Gly LysGlu Glu His Gly Ser Gly 3320 3325 3330 Ala Ala Asp Ala Asn Gln Ala GluGly His Glu Ser Asn Phe Ile 3335 3340 3345 Ala Gln Leu Ala Ser Gln LysHis Thr Arg Lys Asn Thr Gln Ser 3350 3355 3360 Phe Lys Arg Lys Pro GlyGln Ala Asp Asn Glu Arg Ser Met Gly 3365 3370 3375 Asp His Asn Glu ArgVal His Lys Arg Leu Arg Thr Val Asp Thr 3380 3385 3390 Asp Ser His AlaGlu Gln Gly Pro Ala Gln Gln Pro Gln Ala Gln 3395 3400 3405 Val Glu AspAla Asp Ala Phe Glu His Ile Lys Gln Gly Ser Asp 3410 3415 3420 Ala TyrAsp Ala Gln Thr Tyr Asp Val Ala Ser Lys Glu Gln Gln 3425 3430 3435 GlnSer Ala Lys Asp Ser Gly Lys Asp Gln Glu Glu Glu Glu Ile 3440 3445 3450Glu Asp Thr Leu Met Asp Thr Glu Glu Gln Glu Glu Phe Lys Ala 3455 34603465 Ala Asp Val Glu Gln Leu Lys Pro Glu Glu Ile Lys Ser Gly Thr 34703475 3480 Thr Ala Pro Leu Gly Phe Asp Glu Met Glu Val Glu Ile Gln Thr3485 3490 3495 Val Lys Thr Glu Glu Asp Gln Asp Pro Arg Thr Asp Lys AlaHis 3500 3505 3510 Lys Glu Thr Glu Asn Glu Lys Pro Glu Arg Ser Arg GluSer Thr 3515 3520 3525 Ile His Thr Ala His Gln Phe Leu Met Asp Thr IlePhe Gln Pro 3530 3535 3540 Phe Leu Lys Asp Val Asn Glu Leu Arg Gln GluLeu Glu Arg Gln 3545 3550 3555 Leu Glu Met Trp Gln Pro Arg Glu Ser GlyAsn Pro Glu Glu Glu 3560 3565 3570 Lys Val Ala Ala Glu Met Trp Gln SerTyr Leu Ile Leu Thr Ala 3575 3580 3585 Pro Leu Ser Gln Arg Leu Cys GluGlu Leu Arg Leu Ile Leu Glu 3590 3595 3600 Pro Thr Gln Ala Ala Lys LeuLys Gly Asp Tyr Arg Thr Gly Lys 3605 3610 3615 Arg Leu Asn Ile Arg LysVal Ile Pro Tyr Ile Ala Ser Gln Phe 3620 3625 3630 Arg Lys Asp Lys IleTrp Leu Arg Arg Thr Lys Pro Ser Lys Arg 3635 3640 3645 Gln Tyr Gln IleCys Leu Ala Ile Asp Asp Ser Ser Ser Met Val 3650 3655 3660 Asp Asn HisThr Lys Gln Leu Ala Phe Glu Ser Leu Ala Val Ile 3665 3670 3675 Gly AsnAla Leu Thr Leu Leu Glu Val Gly Gln Ile Ala Val Cys 3680 3685 3690 SerPhe Gly Glu Ser Val Lys Leu Leu His Pro Phe His Glu Gln 3695 3700 3705Phe Ser Asp Tyr Ser Gly Ser Gln Ile Leu Arg Leu Cys Lys Phe 3710 37153720 Gln Gln Lys Lys Thr Lys Ile Ala Gln Phe Leu Glu Ser Val Ala 37253730 3735 Asn Met Phe Ala Ala Ala Gln Gln Leu Ser Gln Asn Ile Ser Ser3740 3745 3750 Glu Thr Ala Gln Leu Leu Leu Val Val Ser Asp Gly Arg GlyLeu 3755 3760 3765 Phe Leu Glu Gly Lys Glu Arg Val Leu Ala Ala Val GlnAla Ala 3770 3775 3780 Arg Asn Ala Asn Ile Phe Val Ile Phe Val Val LeuAsp Asn Pro 3785 3790 3795 Ser Ser Arg Asp Ser Ile Leu Asp Ile Lys ValPro Ile Phe Lys 3800 3805 3810 Gly Pro Gly Glu Met Pro Glu Ile Arg SerTyr Met Glu Glu Phe 3815 3820 3825 Pro Phe Pro Tyr Tyr Ile Ile Leu ArgAsp Val Asn Ala Leu Pro 3830 3835 3840 Glu Thr Leu Ser Asp Ala Leu ArgGln Trp Phe Glu Leu Val Thr 3845 3850 3855 Ala Ser Asp His Pro 3860 85384 DNA Homo sapiens CDS (290)..(2434) 8 cttttctcaa gtctctcgttccacctgagg agaaatgccc acagctgtgg aggcgcaggc 60 cactccatct ggtgcccaacgtggatgctt ttctctaggg tgaagggact ctcgagtgtg 120 gtcattgagg acaagtcaacgagagattcc cgagtacgtc tacagtgagc cttgtgggtg 180 aaggtactct acagtgtggtcattgaggac aagttgacga gagagtccca agtacgtcca 240 cggtcagcct tgcggtaagcttgtgtgctt agaggaaccc agggtaacg atg ggg caa 298 Met Gly Gln 1 act gaaagt aaa tat gcc tct tat ctc agc ttt att aaa att ctt tta 346 Thr Glu SerLys Tyr Ala Ser Tyr Leu Ser Phe Ile Lys Ile Leu Leu 5 10 15 aga aga ggggga gtt aga gct tct aca gaa aat cta att acg cta ttt 394 Arg Arg Gly GlyVal Arg Ala Ser Thr Glu Asn Leu Ile Thr Leu Phe 20 25 30 35 caa aca atagaa caa ttc tgc cca tgg ttt cca gaa cag gga act tta 442 Gln Thr Ile GluGln Phe Cys Pro Trp Phe Pro Glu Gln Gly Thr Leu 40 45 50 gat cta aaa gattgg gaa aaa att ggc aaa gaa tta aaa caa gca aat 490 Asp Leu Lys Asp TrpGlu Lys Ile Gly Lys Glu Leu Lys Gln Ala Asn 55 60 65 agg gaa ggt aaa atcatc cca ctt aca gta tgg aat gat tgg gcc att 538 Arg Glu Gly Lys Ile IlePro Leu Thr Val Trp Asn Asp Trp Ala Ile 70 75 80 att aaa gca act tta gaacca ttt caa aca gga gaa gat att gtt tca 586 Ile Lys Ala Thr Leu Glu ProPhe Gln Thr Gly Glu Asp Ile Val Ser 85 90 95 gtt tct gat gcc cct aaa agctgt gta aca gat tgt gaa gaa gag gca 634 Val Ser Asp Ala Pro Lys Ser CysVal Thr Asp Cys Glu Glu Glu Ala 100 105 110 115 ggg aca gaa tcc cag caagga acg gaa agt tca cat tgt aaa tat gta 682 Gly Thr Glu Ser Gln Gln GlyThr Glu Ser Ser His Cys Lys Tyr Val 120 125 130 gca gag tct gta atg gctcag tca acg caa aat gtt gac tac agt caa 730 Ala Glu Ser Val Met Ala GlnSer Thr Gln Asn Val Asp Tyr Ser Gln 135 140 145 tta cag gag ata ata taccct gaa tca tca aaa ttg ggg gaa gga ggt 778 Leu Gln Glu Ile Ile Tyr ProGlu Ser Ser Lys Leu Gly Glu Gly Gly 150 155 160 cca gaa tca ttg ggg ccatca gag cct aaa cca cga tcg cca tca act 826 Pro Glu Ser Leu Gly Pro SerGlu Pro Lys Pro Arg Ser Pro Ser Thr 165 170 175 cct cct ccc gtg gtt cagatg cct gta aca tta caa cct caa acg cag 874 Pro Pro Pro Val Val Gln MetPro Val Thr Leu Gln Pro Gln Thr Gln 180 185 190 195 gtt aga caa gca caaacc cca aga gaa aat caa gta gaa agg gac aga 922 Val Arg Gln Ala Gln ThrPro Arg Glu Asn Gln Val Glu Arg Asp Arg 200 205 210 gtc tct atc ccg gcaatg cca act cag ata cag tat cca caa tat cag 970 Val Ser Ile Pro Ala MetPro Thr Gln Ile Gln Tyr Pro Gln Tyr Gln 215 220 225 ccg gta gaa aat aagacc caa ccg ctg gta gtt tat caa tac cgg ctg 1018 Pro Val Glu Asn Lys ThrGln Pro Leu Val Val Tyr Gln Tyr Arg Leu 230 235 240 cca acc gag ctt cagtat cgg cct cct tca gag gtt caa tac aga cct 1066 Pro Thr Glu Leu Gln TyrArg Pro Pro Ser Glu Val Gln Tyr Arg Pro 245 250 255 caa gcg gtg tgt cctgtg cca aat agc acg gca cca tac cag caa ccc 1114 Gln Ala Val Cys Pro ValPro Asn Ser Thr Ala Pro Tyr Gln Gln Pro 260 265 270 275 aca gcg atg gcgtct aat tca cca gca aca cag gac gcg gcg ctg tat 1162 Thr Ala Met Ala SerAsn Ser Pro Ala Thr Gln Asp Ala Ala Leu Tyr 280 285 290 cct cag ccg cccact gtg aga ctt aat cct aca gca tca cgt agt gga 1210 Pro Gln Pro Pro ThrVal Arg Leu Asn Pro Thr Ala Ser Arg Ser Gly 295 300 305 cag ggt ggt gcactg cat gca gtc att gat gaa gcc aga aaa cag ggc 1258 Gln Gly Gly Ala LeuHis Ala Val Ile Asp Glu Ala Arg Lys Gln Gly 310 315 320 gat ctt gag gcatgg cgg ttc ctg gta att tta caa ctg gta cag gcc 1306 Asp Leu Glu Ala TrpArg Phe Leu Val Ile Leu Gln Leu Val Gln Ala 325 330 335 ggg gaa gag actcaa gta gga gcg cct gcc cga gct gag act aga tgt 1354 Gly Glu Glu Thr GlnVal Gly Ala Pro Ala Arg Ala Glu Thr Arg Cys 340 345 350 355 gaa cct ttcacc atg aaa atg tta aaa gat ata aag gaa gga gtt aaa 1402 Glu Pro Phe ThrMet Lys Met Leu Lys Asp Ile Lys Glu Gly Val Lys 360 365 370 caa tat ggatcc aac tcc cct tat ata aga aca tta tta gat tcc att 1450 Gln Tyr Gly SerAsn Ser Pro Tyr Ile Arg Thr Leu Leu Asp Ser Ile 375 380 385 gct cat ggaaat aga ctt act cct tat gac tgg gaa att ttg gcc aaa 1498 Ala His Gly AsnArg Leu Thr Pro Tyr Asp Trp Glu Ile Leu Ala Lys 390 395 400 tct tcc ctttca tcc tct cag tat cta cag ttt aaa acc tgg tgg att 1546 Ser Ser Leu SerSer Ser Gln Tyr Leu Gln Phe Lys Thr Trp Trp Ile 405 410 415 gat gga gtacaa gaa cag gta cga aaa aat cag gct act aag ccc act 1594 Asp Gly Val GlnGlu Gln Val Arg Lys Asn Gln Ala Thr Lys Pro Thr 420 425 430 435 gtt aatata gac gca gac caa ttg tta gga aca ggt cca aat tgg agc 1642 Val Asn IleAsp Ala Asp Gln Leu Leu Gly Thr Gly Pro Asn Trp Ser 440 445 450 acc attaac caa caa tca gtg atg cag aat gag gct att gaa caa gta 1690 Thr Ile AsnGln Gln Ser Val Met Gln Asn Glu Ala Ile Glu Gln Val 455 460 465 agg gctatt tgc ctc agg gcc tgg gga aaa att cag gac cca gga aca 1738 Arg Ala IleCys Leu Arg Ala Trp Gly Lys Ile Gln Asp Pro Gly Thr 470 475 480 gct ttccct att aat tca att aga caa ggc tct aaa gag cca tat cct 1786 Ala Phe ProIle Asn Ser Ile Arg Gln Gly Ser Lys Glu Pro Tyr Pro 485 490 495 gac tttgtg gca aga tta caa gat gct gct caa aag tct att aca gat 1834 Asp Phe ValAla Arg Leu Gln Asp Ala Ala Gln Lys Ser Ile Thr Asp 500 505 510 515 gacaat gcc cga aaa gtt att gta gaa tta atg gcc tat gaa aat gca 1882 Asp AsnAla Arg Lys Val Ile Val Glu Leu Met Ala Tyr Glu Asn Ala 520 525 530 aatcca gaa tgt cag tcg gcc ata aag cca tta aaa gga aaa gtt cca 1930 Asn ProGlu Cys Gln Ser Ala Ile Lys Pro Leu Lys Gly Lys Val Pro 535 540 545 gcagga gtt gat gta att aca gaa tat gtg aag gct tgt gat ggg att 1978 Ala GlyVal Asp Val Ile Thr Glu Tyr Val Lys Ala Cys Asp Gly Ile 550 555 560 ggagga gct atg cat aag gca atg cta atg gct caa gca atg agg ggg 2026 Gly GlyAla Met His Lys Ala Met Leu Met Ala Gln Ala Met Arg Gly 565 570 575 ctcact cta gga gga caa gtt aga aca ttt ggg aaa aaa tgt tat aat 2074 Leu ThrLeu Gly Gly Gln Val Arg Thr Phe Gly Lys Lys Cys Tyr Asn 580 585 590 595tgt ggt caa atc ggt cat ctg aaa agg agt tgc cca ggc tta aat aaa 2122 CysGly Gln Ile Gly His Leu Lys Arg Ser Cys Pro Gly Leu Asn Lys 600 605 610cag aat ata ata aat caa gct att aca gca aaa aat aaa aag cca tct 2170 GlnAsn Ile Ile Asn Gln Ala Ile Thr Ala Lys Asn Lys Lys Pro Ser 615 620 625ggc ctg tgt cca aaa tgt gga aaa gca aaa cat tgg gcc aat caa tgt 2218 GlyLeu Cys Pro Lys Cys Gly Lys Ala Lys His Trp Ala Asn Gln Cys 630 635 640cat tct aaa ttt gat aaa gat ggg caa cca ttg tct gga aac agg aag 2266 HisSer Lys Phe Asp Lys Asp Gly Gln Pro Leu Ser Gly Asn Arg Lys 645 650 655agg ggc cag cct cag gcc ccc caa caa act ggg gca ttc cca gtt aaa 2314 ArgGly Gln Pro Gln Ala Pro Gln Gln Thr Gly Ala Phe Pro Val Lys 660 665 670675 ctg ttt gtt cct cag ggt ttt caa gga caa caa ccc cta cag aaa ata 2362Leu Phe Val Pro Gln Gly Phe Gln Gly Gln Gln Pro Leu Gln Lys Ile 680 685690 cca cca ctt cag gga gtc agc caa tta caa caa tcc aac agc tgt ccc 2410Pro Pro Leu Gln Gly Val Ser Gln Leu Gln Gln Ser Asn Ser Cys Pro 695 700705 gcg cca cag cag gca gca ccg cag tagatttatg ttccacccaa atggtctttt2464 Ala Pro Gln Gln Ala Ala Pro Gln 710 715 tactccctgg aaagcccccacaaaagattc ctagaggggt atatggcccg ctgccagaag 2524 ggagggtagg cctttgagggagatcaagtc taaatttgaa gggagtccaa attcatactg 2584 gggtaattta ttcagattataaagggggaa ttcagttagt gatcagctcc actgttcccc 2644 ggagtgccaa tccaggtgatagaattgctc aattactgct tttgccttat gttaaaattg 2704 gggaaaacaa aaaggaaagaacaggagggt ttggaagtac caaccctgca ggaaaagctg 2764 cttattgggc taatcaggtctcagaggata gacccgtgtg tacagtcact attcagggaa 2824 agagtttgaa ggattagtggatacccaggc tgatgtttct gtcatcggca taggtactgc 2884 ctcagaagtg tatcaaagtgccatgatttt acattgtcca ggatctgata atcaagaaag 2944 tacggttcag cctgtgatcacttcattcca atcaatttat ggggccgaga cttgttacaa 3004 caatggcatg cagagattactatcccagcc tccctataca gccccaggaa taaaaaaatc 3064 atgactaaaa tgggatagctccctaaaaag ggactaggaa agaagtccca attgaggctg 3124 aaaaaaatca aaaaagaaaaggaatagggc atccttttta ggagcggtca ctgtagagcc 3184 tccaaaaccc attccattaacttgggggaa aaaaaaacaa ctgtatggta aatcagcagc 3244 gcttccaaaa caaaaactggaggctttaca tttattagca aagaaacaat tagaaaaagg 3304 acattgagcc ttcattttcgccttggaatt ctgtttgtaa ttcagaaaaa atccggcaga 3364 tggcgtataa tgccgtaattcaacccatgg gggctctccc accccggttg ccctctccag 3424 ccatggtccc ctttaattataattgatctg aaggattgct tttttaccat tcctctggca 3484 aaacaggatt ttgaaaaatttgcttttacc acaccagcct aaataataaa gaaccagcca 3544 ccaggtttca gtggaaagtattgcctcagg gaatgcttaa tagttcaact atttgtcagc 3604 tcaagctctg caaccagttagagacaagtt ttcagactgt tacatcgttc actatgttga 3664 tattttgtgt gctgcagaaacgagagacaa attaattgac cgttacacat ttctgcagac 3724 agaggttgcc aacgcgggactgacaataac atctgataag attcaaacct ctactccttt 3784 ccgttacttg ggaatgcaggtagaggaaag gaaaattaaa ccacaaaaaa tagaaataag 3844 aaaagacaca ttaaaagcattaaatgagtt tcaaaagttg ctaggagata ctaattggat 3904 ttggagatat taattggatttggccaactc taggcattcc tacttatgcc atgtcaaatt 3964 tgttctcttt cttaagaggggactcggaat taaatagtga aagaacgtta actccagagg 4024 caactaaaga aattaaattaattgaagaaa aaattcggtc agcacaagta aatagaatag 4084 atcacttggc cccactccaaattttgattt ttgctactgc acattcccta acaggcatca 4144 ttgttcaaaa tacagatcttgtggagtggt ccttccttcc tcacagtaca attaagactt 4204 ttacattgta cttggatcaaatggctacat taattggtca gggaagatta tgaataataa 4264 cattgtgtgg aaatgacccagataaaatca ctgttccttt caacaagcaa caggttagac 4324 aagcctttat caattctggtgcatggcaga ttggtcttgc cgattttgtg ggaattattg 4384 acaatcgtta ccccaaaacaaaaatcttcc agtttttaaa attgactact tggattttac 4444 ctaaagttac caaacataagcctttaaaaa atgctctggc agtgtttact gatggttcca 4504 gcaatggaaa agtggcttacaccgggccaa aagaatgagt catcaaaact cagtatcact 4564 tgactcaaag agcagagttggttgccgtca ttacagtgtt aacaagattt taatcagtct 4624 attaacattg tatcagattctgcatatgta gtacaggcta caaaggatat tgagagagcc 4684 ctaatcaaat acattatggatgatcagtta aacccgctgt ttaatttgtt acaacaaaat 4744 gtaagaaaaa gaaatttcccattttatatt actcatattc gagcacacac taatttacca 4804 gggcctttaa ctaaagcaaatgaacaagct gacttgctag tatcatctgc attcatggaa 4864 gcacaagaac ttcatgccttgactcatgta aatgcaatag gattaaaaaa taaatttgat 4924 atcacatgga aacagacaaaaaatattgta caacattgca cccagtgtca gattctacac 4984 ctggccactc aggaggcaagagttaatccc agaggtctat gtcctaatgt gttatggcaa 5044 atggatgtca tgcacgtaccttcatttgga aaattgtcat ttgtccatgt gacagttgat 5104 acttattcac atttcatatgggcaacctgc cagacaggag aaagtacttc ccatgttaaa 5164 agacatttat tatcttgttttcctgtcatg ggagttccag aaaaagttaa aacagacaat 5224 gggccaggtt actgtagtaaagcagttcaa aaattcttaa atcagtggaa aattacacat 5284 acaataggaa ttctctataattcccaagga caggccataa ttgaaagaac taatagaaca 5344 ctcaaagctc aattggttaaacaaaaaaaa aaaaaaaaaa 5384 9 715 PRT Homo sapiens 9 Met Gly Gln Thr GluSer Lys Tyr Ala Ser Tyr Leu Ser Phe Ile Lys 1 5 10 15 Ile Leu Leu ArgArg Gly Gly Val Arg Ala Ser Thr Glu Asn Leu Ile 20 25 30 Thr Leu Phe GlnThr Ile Glu Gln Phe Cys Pro Trp Phe Pro Glu Gln 35 40 45 Gly Thr Leu AspLeu Lys Asp Trp Glu Lys Ile Gly Lys Glu Leu Lys 50 55 60 Gln Ala Asn ArgGlu Gly Lys Ile Ile Pro Leu Thr Val Trp Asn Asp 65 70 75 80 Trp Ala IleIle Lys Ala Thr Leu Glu Pro Phe Gln Thr Gly Glu Asp 85 90 95 Ile Val SerVal Ser Asp Ala Pro Lys Ser Cys Val Thr Asp Cys Glu 100 105 110 Glu GluAla Gly Thr Glu Ser Gln Gln Gly Thr Glu Ser Ser His Cys 115 120 125 LysTyr Val Ala Glu Ser Val Met Ala Gln Ser Thr Gln Asn Val Asp 130 135 140Tyr Ser Gln Leu Gln Glu Ile Ile Tyr Pro Glu Ser Ser Lys Leu Gly 145 150155 160 Glu Gly Gly Pro Glu Ser Leu Gly Pro Ser Glu Pro Lys Pro Arg Ser165 170 175 Pro Ser Thr Pro Pro Pro Val Val Gln Met Pro Val Thr Leu GlnPro 180 185 190 Gln Thr Gln Val Arg Gln Ala Gln Thr Pro Arg Glu Asn GlnVal Glu 195 200 205 Arg Asp Arg Val Ser Ile Pro Ala Met Pro Thr Gln IleGln Tyr Pro 210 215 220 Gln Tyr Gln Pro Val Glu Asn Lys Thr Gln Pro LeuVal Val Tyr Gln 225 230 235 240 Tyr Arg Leu Pro Thr Glu Leu Gln Tyr ArgPro Pro Ser Glu Val Gln 245 250 255 Tyr Arg Pro Gln Ala Val Cys Pro ValPro Asn Ser Thr Ala Pro Tyr 260 265 270 Gln Gln Pro Thr Ala Met Ala SerAsn Ser Pro Ala Thr Gln Asp Ala 275 280 285 Ala Leu Tyr Pro Gln Pro ProThr Val Arg Leu Asn Pro Thr Ala Ser 290 295 300 Arg Ser Gly Gln Gly GlyAla Leu His Ala Val Ile Asp Glu Ala Arg 305 310 315 320 Lys Gln Gly AspLeu Glu Ala Trp Arg Phe Leu Val Ile Leu Gln Leu 325 330 335 Val Gln AlaGly Glu Glu Thr Gln Val Gly Ala Pro Ala Arg Ala Glu 340 345 350 Thr ArgCys Glu Pro Phe Thr Met Lys Met Leu Lys Asp Ile Lys Glu 355 360 365 GlyVal Lys Gln Tyr Gly Ser Asn Ser Pro Tyr Ile Arg Thr Leu Leu 370 375 380Asp Ser Ile Ala His Gly Asn Arg Leu Thr Pro Tyr Asp Trp Glu Ile 385 390395 400 Leu Ala Lys Ser Ser Leu Ser Ser Ser Gln Tyr Leu Gln Phe Lys Thr405 410 415 Trp Trp Ile Asp Gly Val Gln Glu Gln Val Arg Lys Asn Gln AlaThr 420 425 430 Lys Pro Thr Val Asn Ile Asp Ala Asp Gln Leu Leu Gly ThrGly Pro 435 440 445 Asn Trp Ser Thr Ile Asn Gln Gln Ser Val Met Gln AsnGlu Ala Ile 450 455 460 Glu Gln Val Arg Ala Ile Cys Leu Arg Ala Trp GlyLys Ile Gln Asp 465 470 475 480 Pro Gly Thr Ala Phe Pro Ile Asn Ser IleArg Gln Gly Ser Lys Glu 485 490 495 Pro Tyr Pro Asp Phe Val Ala Arg LeuGln Asp Ala Ala Gln Lys Ser 500 505 510 Ile Thr Asp Asp Asn Ala Arg LysVal Ile Val Glu Leu Met Ala Tyr 515 520 525 Glu Asn Ala Asn Pro Glu CysGln Ser Ala Ile Lys Pro Leu Lys Gly 530 535 540 Lys Val Pro Ala Gly ValAsp Val Ile Thr Glu Tyr Val Lys Ala Cys 545 550 555 560 Asp Gly Ile GlyGly Ala Met His Lys Ala Met Leu Met Ala Gln Ala 565 570 575 Met Arg GlyLeu Thr Leu Gly Gly Gln Val Arg Thr Phe Gly Lys Lys 580 585 590 Cys TyrAsn Cys Gly Gln Ile Gly His Leu Lys Arg Ser Cys Pro Gly 595 600 605 LeuAsn Lys Gln Asn Ile Ile Asn Gln Ala Ile Thr Ala Lys Asn Lys 610 615 620Lys Pro Ser Gly Leu Cys Pro Lys Cys Gly Lys Ala Lys His Trp Ala 625 630635 640 Asn Gln Cys His Ser Lys Phe Asp Lys Asp Gly Gln Pro Leu Ser Gly645 650 655 Asn Arg Lys Arg Gly Gln Pro Gln Ala Pro Gln Gln Thr Gly AlaPhe 660 665 670 Pro Val Lys Leu Phe Val Pro Gln Gly Phe Gln Gly Gln GlnPro Leu 675 680 685 Gln Lys Ile Pro Pro Leu Gln Gly Val Ser Gln Leu GlnGln Ser Asn 690 695 700 Ser Cys Pro Ala Pro Gln Gln Ala Ala Pro Gln 705710 715 10 8467 DNA Homo sapiens CDS (1)..(5232) 10 atg gaa gaa aat gaaagc cag aaa tgt gag ccg tgc ctt cct tac tca 48 Met Glu Glu Asn Glu SerGln Lys Cys Glu Pro Cys Leu Pro Tyr Ser 1 5 10 15 gca gac aga aga cagatg cag gaa caa ggc aaa ggc aat ctg cat gta 96 Ala Asp Arg Arg Gln MetGln Glu Gln Gly Lys Gly Asn Leu His Val 20 25 30 aca tca cca gaa gat gcagaa tgc cgc aga acc aag gaa cgc ctt tct 144 Thr Ser Pro Glu Asp Ala GluCys Arg Arg Thr Lys Glu Arg Leu Ser 35 40 45 aat gga aac agt cgt ggt tcagtt tcc aag tct tcc cgc aat atc cca 192 Asn Gly Asn Ser Arg Gly Ser ValSer Lys Ser Ser Arg Asn Ile Pro 50 55 60 agg aga cac acc cta ggg ggg ccccga agt tcc aag gaa ata ctg gga 240 Arg Arg His Thr Leu Gly Gly Pro ArgSer Ser Lys Glu Ile Leu Gly 65 70 75 80 atg caa aca tct gag atg gat cggaag aga gaa gcg ttc cta gaa cat 288 Met Gln Thr Ser Glu Met Asp Arg LysArg Glu Ala Phe Leu Glu His 85 90 95 ctg aag cag aag tac ccc cac cac gcctct gca atc atg ggt cac caa 336 Leu Lys Gln Lys Tyr Pro His His Ala SerAla Ile Met Gly His Gln 100 105 110 gag agg ctg aga gac cag aca agg agcccc aaa ctg tct cac agt cct 384 Glu Arg Leu Arg Asp Gln Thr Arg Ser ProLys Leu Ser His Ser Pro 115 120 125 caa cca ccc agt ctg ggt gac ccg gtcgag cat tta tca gag acg tcc 432 Gln Pro Pro Ser Leu Gly Asp Pro Val GluHis Leu Ser Glu Thr Ser 130 135 140 gct gat tct ttg gaa gcc atg tct gagggg gat gct cca acc cct ttt 480 Ala Asp Ser Leu Glu Ala Met Ser Glu GlyAsp Ala Pro Thr Pro Phe 145 150 155 160 tcc aga ggc agc cgg act cgt gcgagc ctt cct gtg gtg agg tca acc 528 Ser Arg Gly Ser Arg Thr Arg Ala SerLeu Pro Val Val Arg Ser Thr 165 170 175 aac cag acg aaa gaa aga tct ctgggg gtt ctc tat ctc cag tat gga 576 Asn Gln Thr Lys Glu Arg Ser Leu GlyVal Leu Tyr Leu Gln Tyr Gly 180 185 190 gat gaa acc aag cag ctc agg atgccg aat gaa atc aca agt gca gac 624 Asp Glu Thr Lys Gln Leu Arg Met ProAsn Glu Ile Thr Ser Ala Asp 195 200 205 aca atc cgt gct ctc ttc gta agtgcc ttt cca cag cag ctc acc atg 672 Thr Ile Arg Ala Leu Phe Val Ser AlaPhe Pro Gln Gln Leu Thr Met 210 215 220 aaa atg ctg gaa tcg ccc agt gtcgcc att tac atc aaa gat gaa agc 720 Lys Met Leu Glu Ser Pro Ser Val AlaIle Tyr Ile Lys Asp Glu Ser 225 230 235 240 aga aat gtc tat tat gaa ttaaat gat gta agg aac att caa gac aga 768 Arg Asn Val Tyr Tyr Glu Leu AsnAsp Val Arg Asn Ile Gln Asp Arg 245 250 255 tca ctc ctc aaa gtg tac aacaag gat cct gca cat gcg ttt aat cac 816 Ser Leu Leu Lys Val Tyr Asn LysAsp Pro Ala His Ala Phe Asn His 260 265 270 aca cca aaa act atg aat ggagac atg agg atg cag aga gaa ctt gtt 864 Thr Pro Lys Thr Met Asn Gly AspMet Arg Met Gln Arg Glu Leu Val 275 280 285 tat gca aga gga gat ggc cctggg gcc cct cgc ccc gga tct act gct 912 Tyr Ala Arg Gly Asp Gly Pro GlyAla Pro Arg Pro Gly Ser Thr Ala 290 295 300 cat cca ccc cat gcg att ccaaat tcc cca ccg tct act cca gtg ccc 960 His Pro Pro His Ala Ile Pro AsnSer Pro Pro Ser Thr Pro Val Pro 305 310 315 320 cat tcc atg ccc ccc tccccg tcc aga att cct tat ggg ggc acc cgc 1008 His Ser Met Pro Pro Ser ProSer Arg Ile Pro Tyr Gly Gly Thr Arg 325 330 335 tcc atg gtt gtt cct ggcaat gcc acc atc ccc agg gac aga atc tcc 1056 Ser Met Val Val Pro Gly AsnAla Thr Ile Pro Arg Asp Arg Ile Ser 340 345 350 agc ctg cca gtc tcc agaccc atc tct cca agc cca agc gcc att tta 1104 Ser Leu Pro Val Ser Arg ProIle Ser Pro Ser Pro Ser Ala Ile Leu 355 360 365 gaa aga aga gat gtc aagcct gat gaa gac atg agt ggc aaa aac att 1152 Glu Arg Arg Asp Val Lys ProAsp Glu Asp Met Ser Gly Lys Asn Ile 370 375 380 gca atg tac aga aat gagggt ttc tat gct gat cct tac ctt tat cac 1200 Ala Met Tyr Arg Asn Glu GlyPhe Tyr Ala Asp Pro Tyr Leu Tyr His 385 390 395 400 gag gga cgg atg agcata gcc tca tcc cat ggt gga cac cca ctg gat 1248 Glu Gly Arg Met Ser IleAla Ser Ser His Gly Gly His Pro Leu Asp 405 410 415 gtc ccc gac cac atcatt gca tat cac cgc acc gcc atc cgg tca gcg 1296 Val Pro Asp His Ile IleAla Tyr His Arg Thr Ala Ile Arg Ser Ala 420 425 430 agt gct tat tgt aacccc tca atg caa gcg gaa atg cat atg gaa caa 1344 Ser Ala Tyr Cys Asn ProSer Met Gln Ala Glu Met His Met Glu Gln 435 440 445 tca ctg tac aga cagaaa tca agg aaa tat ccg gat agc cat ttg cct 1392 Ser Leu Tyr Arg Gln LysSer Arg Lys Tyr Pro Asp Ser His Leu Pro 450 455 460 aca ctg ggc tcc aaaaca ccc cct gcc tct cct cac aga gtc agt gac 1440 Thr Leu Gly Ser Lys ThrPro Pro Ala Ser Pro His Arg Val Ser Asp 465 470 475 480 ctg agg atg atagac atg cac gct cac tat aat gcc cac ggc ccc cct 1488 Leu Arg Met Ile AspMet His Ala His Tyr Asn Ala His Gly Pro Pro 485 490 495 cac acc atg cagcca gac cgg gcc tct ccg agc cgc cag gcc ttt aaa 1536 His Thr Met Gln ProAsp Arg Ala Ser Pro Ser Arg Gln Ala Phe Lys 500 505 510 aag gag cca ggcacc ttg gtg tat ata gaa aag cca cgg agc gct gca 1584 Lys Glu Pro Gly ThrLeu Val Tyr Ile Glu Lys Pro Arg Ser Ala Ala 515 520 525 gga tta tcc agcctt gta gac ctc ggc cct cct cta atg gag aag caa 1632 Gly Leu Ser Ser LeuVal Asp Leu Gly Pro Pro Leu Met Glu Lys Gln 530 535 540 gtt ttt gcc tacagc acg gcg aca ata ccc aaa gac aga gag acc aga 1680 Val Phe Ala Tyr SerThr Ala Thr Ile Pro Lys Asp Arg Glu Thr Arg 545 550 555 560 gag agg atgcaa gcc atg gag aaa cag att gcc agt tta act ggc ctt 1728 Glu Arg Met GlnAla Met Glu Lys Gln Ile Ala Ser Leu Thr Gly Leu 565 570 575 gtt cag tctgcg ctt ttt aaa ggg ccc att aca agt tat agc aaa gat 1776 Val Gln Ser AlaLeu Phe Lys Gly Pro Ile Thr Ser Tyr Ser Lys Asp 580 585 590 gcg tct agcgag aaa atg atg aaa acc aca gcc aac agg aac cac aca 1824 Ala Ser Ser GluLys Met Met Lys Thr Thr Ala Asn Arg Asn His Thr 595 600 605 gat agt gcagga acg ccc cat gtg tct ggt ggg aag atg ctc agt gct 1872 Asp Ser Ala GlyThr Pro His Val Ser Gly Gly Lys Met Leu Ser Ala 610 615 620 ctg gag tccacg gtg cct ccc agc cag cct cca cct gtg ggc acc tca 1920 Leu Glu Ser ThrVal Pro Pro Ser Gln Pro Pro Pro Val Gly Thr Ser 625 630 635 640 gcc atccac atg agc ctg ctt gag atg agg cgg agc gtg gcg gaa ctc 1968 Ala Ile HisMet Ser Leu Leu Glu Met Arg Arg Ser Val Ala Glu Leu 645 650 655 agg ctccag ctc cag cag atg cgg cag ctc cag ctg cag aac cag gag 2016 Arg Leu GlnLeu Gln Gln Met Arg Gln Leu Gln Leu Gln Asn Gln Glu 660 665 670 ttg ctgagg gca atg atg aag aag gcc gag ctg gaa atc agt ggc aaa 2064 Leu Leu ArgAla Met Met Lys Lys Ala Glu Leu Glu Ile Ser Gly Lys 675 680 685 gtg atggaa aca atg aag aga ctg gag gat ccc gtg cag cga cag cgc 2112 Val Met GluThr Met Lys Arg Leu Glu Asp Pro Val Gln Arg Gln Arg 690 695 700 gtc ctagtg gag caa gag aga caa aaa tat ctt cat gag gaa gag aag 2160 Val Leu ValGlu Gln Glu Arg Gln Lys Tyr Leu His Glu Glu Glu Lys 705 710 715 720 atcgtc aag aag ttg tgc gag ttg gaa gac ttt gtt gaa gac ttg aag 2208 Ile ValLys Lys Leu Cys Glu Leu Glu Asp Phe Val Glu Asp Leu Lys 725 730 735 aaggac tcc acg gca gcc agc cga ttg gtt act ctg aaa gac gtg gaa 2256 Lys AspSer Thr Ala Ala Ser Arg Leu Val Thr Leu Lys Asp Val Glu 740 745 750 gacggg gct ttc ctc ctg cgt caa gtg gga gag gct gta gct acc ctg 2304 Asp GlyAla Phe Leu Leu Arg Gln Val Gly Glu Ala Val Ala Thr Leu 755 760 765 aaagga gaa ttt cca acc tta caa aac aag atg cga gcc atc ctg cgc 2352 Lys GlyGlu Phe Pro Thr Leu Gln Asn Lys Met Arg Ala Ile Leu Arg 770 775 780 atagaa gtg gag gcc gtg cgg ttt ctg aag gag gag cca cac aag ctg 2400 Ile GluVal Glu Ala Val Arg Phe Leu Lys Glu Glu Pro His Lys Leu 785 790 795 800gac agt ctc ctg aag cgt gtg cgc agc atg aca gac gtc ctg acc atg 2448 AspSer Leu Leu Lys Arg Val Arg Ser Met Thr Asp Val Leu Thr Met 805 810 815ctg cgg aga cat gtc act gat ggg ctc ctg aaa ggc acg gac gca gcc 2496 LeuArg Arg His Val Thr Asp Gly Leu Leu Lys Gly Thr Asp Ala Ala 820 825 830caa gcc gca cag tac atg gct atg gaa aag gcc aca gcc gca gaa gtc 2544 GlnAla Ala Gln Tyr Met Ala Met Glu Lys Ala Thr Ala Ala Glu Val 835 840 845ctg aag agt cag gag gag gca gcc cac acc tcc ggc cag ccc ttc cac 2592 LeuLys Ser Gln Glu Glu Ala Ala His Thr Ser Gly Gln Pro Phe His 850 855 860agc aca ggt gcc cct ggc gat gcg aag tcg gaa gtg gtg cct ttg tcc 2640 SerThr Gly Ala Pro Gly Asp Ala Lys Ser Glu Val Val Pro Leu Ser 865 870 875880 ggc atg atg gtt cgc cac gcg cag agc tcc cct gtg gtc atc cag ccc 2688Gly Met Met Val Arg His Ala Gln Ser Ser Pro Val Val Ile Gln Pro 885 890895 tcc cag cac tcc gtg gcc ctg ctg aac cct gct cag aac ttg cct cac 2736Ser Gln His Ser Val Ala Leu Leu Asn Pro Ala Gln Asn Leu Pro His 900 905910 gtg gcc agc tcc cca gcc gtc ccc cag gaa gca acc tcc act ctg cag 2784Val Ala Ser Ser Pro Ala Val Pro Gln Glu Ala Thr Ser Thr Leu Gln 915 920925 atg tcg cag gct ccg cag tcc cca cag ata ccc atg aat ggg tct gcc 2832Met Ser Gln Ala Pro Gln Ser Pro Gln Ile Pro Met Asn Gly Ser Ala 930 935940 atg cag agc ttg ttc att gaa gaa atc cac agt gtg agt gcc aag aac 2880Met Gln Ser Leu Phe Ile Glu Glu Ile His Ser Val Ser Ala Lys Asn 945 950955 960 agg gca gtg tct atc gag aaa gca gaa aag aaa tgg gag gaa aaa agg2928 Arg Ala Val Ser Ile Glu Lys Ala Glu Lys Lys Trp Glu Glu Lys Arg 965970 975 caa aat ctg gat cac tat aat ggg aaa gag ttt gag aag ctc cta gaa2976 Gln Asn Leu Asp His Tyr Asn Gly Lys Glu Phe Glu Lys Leu Leu Glu 980985 990 gaa gct cag gcc aat atc atg aag tca ata cca aat ctg gag atg ccg3024 Glu Ala Gln Ala Asn Ile Met Lys Ser Ile Pro Asn Leu Glu Met Pro 9951000 1005 cca gcc aca ggc cca ctg cca agg gga gat gcc cca gtg gac aag3069 Pro Ala Thr Gly Pro Leu Pro Arg Gly Asp Ala Pro Val Asp Lys 10101015 1020 gtg gaa ctt tca gaa gat tct cca aat tcg gaa cag gac ttg gaa3114 Val Glu Leu Ser Glu Asp Ser Pro Asn Ser Glu Gln Asp Leu Glu 10251030 1035 aag ctg ggg gga aag tcg ccc cct cct cct ccg cca cct cct cgt3159 Lys Leu Gly Gly Lys Ser Pro Pro Pro Pro Pro Pro Pro Pro Arg 10401045 1050 cga agc tac ctg cca gga tcg gga ctc acc acc acg agg tca ggc3204 Arg Ser Tyr Leu Pro Gly Ser Gly Leu Thr Thr Thr Arg Ser Gly 10551060 1065 gat gtg gtc tac acc ggc aga aag gag aac atc acc gct aag gca3249 Asp Val Val Tyr Thr Gly Arg Lys Glu Asn Ile Thr Ala Lys Ala 10701075 1080 agc agt gaa gat gct gga cca agc cca cag acc aga gct aca aaa3294 Ser Ser Glu Asp Ala Gly Pro Ser Pro Gln Thr Arg Ala Thr Lys 10851090 1095 tat cca gca gag gag cct gct tca gcc tgg acc cca tcc cca ccg3339 Tyr Pro Ala Glu Glu Pro Ala Ser Ala Trp Thr Pro Ser Pro Pro 11001105 1110 cct gtc acc acc tcc tcc tca aag gat gag gag gaa gaa gaa gaa3384 Pro Val Thr Thr Ser Ser Ser Lys Asp Glu Glu Glu Glu Glu Glu 11151120 1125 gaa gga gac aaa ata atg gca gaa ctc cag gca ttc cag aag tgt3429 Glu Gly Asp Lys Ile Met Ala Glu Leu Gln Ala Phe Gln Lys Cys 11301135 1140 tcc ttt atg gat gta aat tca aac agt cat gct gag cca tcc cgg3474 Ser Phe Met Asp Val Asn Ser Asn Ser His Ala Glu Pro Ser Arg 11451150 1155 gct gac agt cac gtt aaa gac act agg tcg ggc gcc aca gtg cca3519 Ala Asp Ser His Val Lys Asp Thr Arg Ser Gly Ala Thr Val Pro 11601165 1170 ccc aag gag aag aag aat ttg gaa ttt ttc cat gaa gat gta cgg3564 Pro Lys Glu Lys Lys Asn Leu Glu Phe Phe His Glu Asp Val Arg 11751180 1185 aaa tct gat gtt gaa tat gaa aat ggc ccc caa atg gaa ttc caa3609 Lys Ser Asp Val Glu Tyr Glu Asn Gly Pro Gln Met Glu Phe Gln 11901195 1200 aag gtt acc aca ggg gct gta aga cct agt gac cct cct aag tgg3654 Lys Val Thr Thr Gly Ala Val Arg Pro Ser Asp Pro Pro Lys Trp 12051210 1215 gaa aga gga atg gag aat agt att tct gat gca tca aga aca tca3699 Glu Arg Gly Met Glu Asn Ser Ile Ser Asp Ala Ser Arg Thr Ser 12201225 1230 gaa tat aaa act gag atc ata atg aag gaa aat tcc ata tcc aat3744 Glu Tyr Lys Thr Glu Ile Ile Met Lys Glu Asn Ser Ile Ser Asn 12351240 1245 atg agt tta ctc aga gac agt aga aac tat tcc cag gaa act gtg3789 Met Ser Leu Leu Arg Asp Ser Arg Asn Tyr Ser Gln Glu Thr Val 12501255 1260 cct aag gcc agt ttc ggt ttc tct ggc att agt cca tta gaa gat3834 Pro Lys Ala Ser Phe Gly Phe Ser Gly Ile Ser Pro Leu Glu Asp 12651270 1275 gaa ata aac aaa ggg tct aaa atc tca ggc ctg caa tac tct ata3879 Glu Ile Asn Lys Gly Ser Lys Ile Ser Gly Leu Gln Tyr Ser Ile 12801285 1290 cct gac acc gag aac cag acg ctg aat tac gga aag aca aag gag3924 Pro Asp Thr Glu Asn Gln Thr Leu Asn Tyr Gly Lys Thr Lys Glu 12951300 1305 atg gaa aag caa aat acg gat aag tgt cac gtt tcc tct cac act3969 Met Glu Lys Gln Asn Thr Asp Lys Cys His Val Ser Ser His Thr 13101315 1320 aga cta aca gaa tca agc gtg cat gat ttt aaa aca gaa gat caa4014 Arg Leu Thr Glu Ser Ser Val His Asp Phe Lys Thr Glu Asp Gln 13251330 1335 gag gtt atc acg aca gat ttt ggc caa gtt gtt cta aga ccc aag4059 Glu Val Ile Thr Thr Asp Phe Gly Gln Val Val Leu Arg Pro Lys 13401345 1350 gag gca agg cat gct aac gtg aac cct aat gag gat gga gaa tca4104 Glu Ala Arg His Ala Asn Val Asn Pro Asn Glu Asp Gly Glu Ser 13551360 1365 agt tca agt tct ccc act gaa gaa aat gca gcc act gac aat att4149 Ser Ser Ser Ser Pro Thr Glu Glu Asn Ala Ala Thr Asp Asn Ile 13701375 1380 gcc ttc atg att acc gaa acc act gtc cag gtt ctt tcc agt ggg4194 Ala Phe Met Ile Thr Glu Thr Thr Val Gln Val Leu Ser Ser Gly 13851390 1395 gag gtg cat gat att gtt agc caa aag gga gaa gac ata cag acg4239 Glu Val His Asp Ile Val Ser Gln Lys Gly Glu Asp Ile Gln Thr 14001405 1410 gtt aat atc gat gcc aga aaa gag atg acc ccc cga caa gaa ggg4284 Val Asn Ile Asp Ala Arg Lys Glu Met Thr Pro Arg Gln Glu Gly 14151420 1425 act gac aat gag gat cca gtc gtg tgc ctg gac aag aaa cca gtg4329 Thr Asp Asn Glu Asp Pro Val Val Cys Leu Asp Lys Lys Pro Val 14301435 1440 atc atc att ttc gat gag ccc atg gac atc cgg tct gcc tat aag4374 Ile Ile Ile Phe Asp Glu Pro Met Asp Ile Arg Ser Ala Tyr Lys 14451450 1455 aga ctt tca act atc ttt gag gaa tgt gat gag gaa tta gag aga4419 Arg Leu Ser Thr Ile Phe Glu Glu Cys Asp Glu Glu Leu Glu Arg 14601465 1470 atg atg atg gag gaa aag ata gag gag gag gaa gag gag gaa aat4464 Met Met Met Glu Glu Lys Ile Glu Glu Glu Glu Glu Glu Glu Asn 14751480 1485 ggg gat tct gta gtc cag aat aat aac act tcc cag atg tct cat4509 Gly Asp Ser Val Val Gln Asn Asn Asn Thr Ser Gln Met Ser His 14901495 1500 aag aag gtg gcc cca ggc aat ctt aga acc gga caa cag gtg gaa4554 Lys Lys Val Ala Pro Gly Asn Leu Arg Thr Gly Gln Gln Val Glu 15051510 1515 aca aag tca cag cca cac tcc ctg gcc aca gag acc aga aac cca4599 Thr Lys Ser Gln Pro His Ser Leu Ala Thr Glu Thr Arg Asn Pro 15201525 1530 gga gga cag gaa atg aac aga acg gag ctg aac aag ttc agc cac4644 Gly Gly Gln Glu Met Asn Arg Thr Glu Leu Asn Lys Phe Ser His 15351540 1545 gtg gat tct cca aat tcg gaa tgc aag ggt gag gac gcg acc gat4689 Val Asp Ser Pro Asn Ser Glu Cys Lys Gly Glu Asp Ala Thr Asp 15501555 1560 gac cag ttt gaa agc ccc aag aaa aag ttt aaa ttc aaa ttc cct4734 Asp Gln Phe Glu Ser Pro Lys Lys Lys Phe Lys Phe Lys Phe Pro 15651570 1575 aag aag caa ctc gcc gct ctc act caa gcc att cgc acc gga act4779 Lys Lys Gln Leu Ala Ala Leu Thr Gln Ala Ile Arg Thr Gly Thr 15801585 1590 aaa aca ggg aag aag act ttg caa gtg gta gtc tat gaa gaa gag4824 Lys Thr Gly Lys Lys Thr Leu Gln Val Val Val Tyr Glu Glu Glu 15951600 1605 gaa gag gat ggc acc ctg aaa cag cac aaa gaa gcc aag cgc ttc4869 Glu Glu Asp Gly Thr Leu Lys Gln His Lys Glu Ala Lys Arg Phe 16101615 1620 gaa atc gct agg tct caa cct gaa gac acc cct gaa aac aca gtg4914 Glu Ile Ala Arg Ser Gln Pro Glu Asp Thr Pro Glu Asn Thr Val 16251630 1635 agg agg caa gag cag ccc agc atc gag agt aca tct ccg att tca4959 Arg Arg Gln Glu Gln Pro Ser Ile Glu Ser Thr Ser Pro Ile Ser 16401645 1650 aga act gat gaa att aga aaa aac acc tac aga aca ttg gat agc5004 Arg Thr Asp Glu Ile Arg Lys Asn Thr Tyr Arg Thr Leu Asp Ser 16551660 1665 ctg gag cag acc att aaa cag ctc gaa aat aca atc agt gaa atg5049 Leu Glu Gln Thr Ile Lys Gln Leu Glu Asn Thr Ile Ser Glu Met 16701675 1680 agt ccc aaa gcc cta gtt gat acc tca tgt tct tcc aac aga gat5094 Ser Pro Lys Ala Leu Val Asp Thr Ser Cys Ser Ser Asn Arg Asp 16851690 1695 tct gtt gca agt tca tcc cac ata gcc caa gag gcc tct ccc cga5139 Ser Val Ala Ser Ser Ser His Ile Ala Gln Glu Ala Ser Pro Arg 17001705 1710 ccc ttg cta gtt ccg gat gaa ggt ccc act gcc cta gag ccc cct5184 Pro Leu Leu Val Pro Asp Glu Gly Pro Thr Ala Leu Glu Pro Pro 17151720 1725 acg tcg ata cct tca gct tca cgt aag gta tct tgg tct gct gga5229 Thr Ser Ile Pro Ser Ala Ser Arg Lys Val Ser Trp Ser Ala Gly 17301735 1740 aaa tgaaaagacc cagctgcttt cctaaatctg ccataatcac cattagtgaa5282 Lys aggtgtcttg taacttaatt gctttctttc aggtggcttt tttttttttgtctgttcgcc 5342 atgaaaccct tctttcatac tttctccctc accttccaaa caacaacaactaggtatcta 5402 acagctaatc agttctgttt ttgcctctgt tgctgactgg tgttgggtaaacacgaggct 5462 gctgggtcag ccatgtgctg ttgaaatggt tgctctgata ctcacattaaaatccgtttg 5522 atcagtagtg agcagttgat tctgtttgat tcttctgatt aaccccagttggtgtctcct 5582 agatctgtcc tgcatgtagg gctgtggctt ctcaccttga gcttctctgcacatcgtggg 5642 gcagcctcac agatgaccta ctcatgcgct tctccttctc ttccccctctcactggtcct 5702 tcccacaggg ctccagcggg gccccacaga cgagcaggat gcctgtccccatgagtgcca 5762 agaacagacc cggaaccctg gacaaacccg gcaagcagtc caaactgcaggatccccgcc 5822 aatatcgtca ggtagtttta ccttaaaccc acttttggat ggacgctatttcagttaagc 5882 aagtcactga cttagtttat accaaatatt gtgctttctt tgtaagataacggtttacat 5942 agacatcctg gatctggggg catgaagaaa gtctaaataa acctttgttacactttttta 6002 ccacgctttt gcatgcttgc aataaaacat cttttacttt gtgactccaaactccaaatt 6062 ttaactgtta acacacggtg ccagaccagg tggcttttct ttggtgaatgtagtgtttca 6122 tctgaacacc tcgggaagca gagacaaacc aacctgtggt tgaactgcccttaacgtcac 6182 cactactaac gtctatgttg actgtattgt gttagaagca cattaacactccgtcacaat 6242 gcccgacccc caccccagta attatccaga cgcatggccc acctggcacacaggaaatgg 6302 tagagctgga atgatgggac tcctctcaca aatgtattct tcctttcctcctttcccgtc 6362 catcctttgc tatgtacatg gggggtttct accaggtcca gtagagcacaacaagactta 6422 gctcaggcct tgaactgtgt ttggttggtt ttctttgatt gaattattctcagaagggct 6482 gtgttgccag gccctgtggg ttgatcatgt gaccgccttt ctgacaaaatgtctcccgcc 6542 atctttattt gcaggctaat ggaagtgcta agaaatctgg tggggactttaagcctactt 6602 ccccctcctt acctgcttct aagattccag ccctttctcc cagctctgggaaaagcagtt 6662 ctctgccctc ttctagtggt gacagctcta acctccctaa tccacctgctactaaaccat 6722 cgattgcttc taaccctctc agcccccaaa caggaccacc tgctcactctgcctccctca 6782 tcccttctgt ctctaatggc tctttgaagt ttcagagcct cactcatacaggtaaaggtc 6842 accatctttc attctcaccg cagagtcaaa atggccgagc accccctcctttgtcatttt 6902 cctcctcccc tccttctcct gcctcctccg tctcactgaa tcaaggtgccaagggcacca 6962 ggaccatcca tactcccagc ctcaccagct acaaggcaca gaatggaagttcaagcaaag 7022 ccaccccatc cacagcaaaa gaaacctctt aaaggtcaaa tcctattaggcacaagtcgg 7082 agttacattt aaaaaaaatt aacagtctac aacaactgtt ttcacaagagaatgtaacat 7142 attgctgtat cgtttgaggc ttaatgctaa atatgtgcta aatactggattaatagattt 7202 cagtaaagct cgttcgtttt gtttggtttt ctttttacct agttgctatagtgtctacag 7262 tctatactca atacctataa aatgcagtaa gcatgtgtta cagaaagaggttctggtggg 7322 agagaaaggt gcgtgtgaga caggagaatt gtcttaagca tataaaacatgtatgattcc 7382 agaattttag tatgttttgt ataaaactat ttttcattac ggagactagaagtgaacaga 7442 gaattacaca agtgtgacta tacaaattgt aaaacagata ctataatatttccttttatt 7502 ttagtgttat ttagctttat tacagatttc tatttttgtc aaaacttcatggttcctttc 7562 aagatctttt ttgccaaaac attttgatac tatagcattg tacatttgaaagtagtgttc 7622 tagactataa aaccaatgaa cttctacatg agccctacag acaggcatgtgtagaaggca 7682 atttatcaaa cctattgcac tgccatgaaa agtgtgtata ataatttgctagcccaagca 7742 agctagtttt ctttgcttgc ttcttttctt tcttttttcc ttcctttttttttttttttt 7802 cttttttaac atgttgagat tctctagttg ttttctttgg cgtatctaaccccttctttt 7862 gttttctgag acctggtaac ccacgctctt gcattgtgga ttttaaaatgtatactctgt 7922 acggttctgt aaaccgaaaa acttttgtaa atatataaat atacatagacataaaaatac 7982 tgtatgtgac agcacataga gtagttttcc cacaccaaag ttaatttttatgcatgcttt 8042 aaaagtatat atcgggaccg gcagaaatgg aagtatccat acatttttaaaaagcaacaa 8102 gtttgcacag ctagagtgtt tttgtaaata aatgtatttg tataacacagtcatgtaata 8162 tacagaacta taagcagaga ctttgcaaaa ctaaataaag ggctgcatgcttattatttt 8222 ttgtaccttg tcactataac tacttcctag tcaaagaacg aaatgtaactgttaccgagt 8282 taaatgtttt tccgctttga gggatgtaac cacatccact cagaggacactacttttctg 8342 aaagctctgg ggtgactaat gatgagttcc taataaatta attgcaagtgtggtgccttg 8402 gaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaaaaaaaaaaaa 8462 aaaaa 8467 11 1744 PRT Homo sapiens 11 Met Glu Glu AsnGlu Ser Gln Lys Cys Glu Pro Cys Leu Pro Tyr Ser 1 5 10 15 Ala Asp ArgArg Gln Met Gln Glu Gln Gly Lys Gly Asn Leu His Val 20 25 30 Thr Ser ProGlu Asp Ala Glu Cys Arg Arg Thr Lys Glu Arg Leu Ser 35 40 45 Asn Gly AsnSer Arg Gly Ser Val Ser Lys Ser Ser Arg Asn Ile Pro 50 55 60 Arg Arg HisThr Leu Gly Gly Pro Arg Ser Ser Lys Glu Ile Leu Gly 65 70 75 80 Met GlnThr Ser Glu Met Asp Arg Lys Arg Glu Ala Phe Leu Glu His 85 90 95 Leu LysGln Lys Tyr Pro His His Ala Ser Ala Ile Met Gly His Gln 100 105 110 GluArg Leu Arg Asp Gln Thr Arg Ser Pro Lys Leu Ser His Ser Pro 115 120 125Gln Pro Pro Ser Leu Gly Asp Pro Val Glu His Leu Ser Glu Thr Ser 130 135140 Ala Asp Ser Leu Glu Ala Met Ser Glu Gly Asp Ala Pro Thr Pro Phe 145150 155 160 Ser Arg Gly Ser Arg Thr Arg Ala Ser Leu Pro Val Val Arg SerThr 165 170 175 Asn Gln Thr Lys Glu Arg Ser Leu Gly Val Leu Tyr Leu GlnTyr Gly 180 185 190 Asp Glu Thr Lys Gln Leu Arg Met Pro Asn Glu Ile ThrSer Ala Asp 195 200 205 Thr Ile Arg Ala Leu Phe Val Ser Ala Phe Pro GlnGln Leu Thr Met 210 215 220 Lys Met Leu Glu Ser Pro Ser Val Ala Ile TyrIle Lys Asp Glu Ser 225 230 235 240 Arg Asn Val Tyr Tyr Glu Leu Asn AspVal Arg Asn Ile Gln Asp Arg 245 250 255 Ser Leu Leu Lys Val Tyr Asn LysAsp Pro Ala His Ala Phe Asn His 260 265 270 Thr Pro Lys Thr Met Asn GlyAsp Met Arg Met Gln Arg Glu Leu Val 275 280 285 Tyr Ala Arg Gly Asp GlyPro Gly Ala Pro Arg Pro Gly Ser Thr Ala 290 295 300 His Pro Pro His AlaIle Pro Asn Ser Pro Pro Ser Thr Pro Val Pro 305 310 315 320 His Ser MetPro Pro Ser Pro Ser Arg Ile Pro Tyr Gly Gly Thr Arg 325 330 335 Ser MetVal Val Pro Gly Asn Ala Thr Ile Pro Arg Asp Arg Ile Ser 340 345 350 SerLeu Pro Val Ser Arg Pro Ile Ser Pro Ser Pro Ser Ala Ile Leu 355 360 365Glu Arg Arg Asp Val Lys Pro Asp Glu Asp Met Ser Gly Lys Asn Ile 370 375380 Ala Met Tyr Arg Asn Glu Gly Phe Tyr Ala Asp Pro Tyr Leu Tyr His 385390 395 400 Glu Gly Arg Met Ser Ile Ala Ser Ser His Gly Gly His Pro LeuAsp 405 410 415 Val Pro Asp His Ile Ile Ala Tyr His Arg Thr Ala Ile ArgSer Ala 420 425 430 Ser Ala Tyr Cys Asn Pro Ser Met Gln Ala Glu Met HisMet Glu Gln 435 440 445 Ser Leu Tyr Arg Gln Lys Ser Arg Lys Tyr Pro AspSer His Leu Pro 450 455 460 Thr Leu Gly Ser Lys Thr Pro Pro Ala Ser ProHis Arg Val Ser Asp 465 470 475 480 Leu Arg Met Ile Asp Met His Ala HisTyr Asn Ala His Gly Pro Pro 485 490 495 His Thr Met Gln Pro Asp Arg AlaSer Pro Ser Arg Gln Ala Phe Lys 500 505 510 Lys Glu Pro Gly Thr Leu ValTyr Ile Glu Lys Pro Arg Ser Ala Ala 515 520 525 Gly Leu Ser Ser Leu ValAsp Leu Gly Pro Pro Leu Met Glu Lys Gln 530 535 540 Val Phe Ala Tyr SerThr Ala Thr Ile Pro Lys Asp Arg Glu Thr Arg 545 550 555 560 Glu Arg MetGln Ala Met Glu Lys Gln Ile Ala Ser Leu Thr Gly Leu 565 570 575 Val GlnSer Ala Leu Phe Lys Gly Pro Ile Thr Ser Tyr Ser Lys Asp 580 585 590 AlaSer Ser Glu Lys Met Met Lys Thr Thr Ala Asn Arg Asn His Thr 595 600 605Asp Ser Ala Gly Thr Pro His Val Ser Gly Gly Lys Met Leu Ser Ala 610 615620 Leu Glu Ser Thr Val Pro Pro Ser Gln Pro Pro Pro Val Gly Thr Ser 625630 635 640 Ala Ile His Met Ser Leu Leu Glu Met Arg Arg Ser Val Ala GluLeu 645 650 655 Arg Leu Gln Leu Gln Gln Met Arg Gln Leu Gln Leu Gln AsnGln Glu 660 665 670 Leu Leu Arg Ala Met Met Lys Lys Ala Glu Leu Glu IleSer Gly Lys 675 680 685 Val Met Glu Thr Met Lys Arg Leu Glu Asp Pro ValGln Arg Gln Arg 690 695 700 Val Leu Val Glu Gln Glu Arg Gln Lys Tyr LeuHis Glu Glu Glu Lys 705 710 715 720 Ile Val Lys Lys Leu Cys Glu Leu GluAsp Phe Val Glu Asp Leu Lys 725 730 735 Lys Asp Ser Thr Ala Ala Ser ArgLeu Val Thr Leu Lys Asp Val Glu 740 745 750 Asp Gly Ala Phe Leu Leu ArgGln Val Gly Glu Ala Val Ala Thr Leu 755 760 765 Lys Gly Glu Phe Pro ThrLeu Gln Asn Lys Met Arg Ala Ile Leu Arg 770 775 780 Ile Glu Val Glu AlaVal Arg Phe Leu Lys Glu Glu Pro His Lys Leu 785 790 795 800 Asp Ser LeuLeu Lys Arg Val Arg Ser Met Thr Asp Val Leu Thr Met 805 810 815 Leu ArgArg His Val Thr Asp Gly Leu Leu Lys Gly Thr Asp Ala Ala 820 825 830 GlnAla Ala Gln Tyr Met Ala Met Glu Lys Ala Thr Ala Ala Glu Val 835 840 845Leu Lys Ser Gln Glu Glu Ala Ala His Thr Ser Gly Gln Pro Phe His 850 855860 Ser Thr Gly Ala Pro Gly Asp Ala Lys Ser Glu Val Val Pro Leu Ser 865870 875 880 Gly Met Met Val Arg His Ala Gln Ser Ser Pro Val Val Ile GlnPro 885 890 895 Ser Gln His Ser Val Ala Leu Leu Asn Pro Ala Gln Asn LeuPro His 900 905 910 Val Ala Ser Ser Pro Ala Val Pro Gln Glu Ala Thr SerThr Leu Gln 915 920 925 Met Ser Gln Ala Pro Gln Ser Pro Gln Ile Pro MetAsn Gly Ser Ala 930 935 940 Met Gln Ser Leu Phe Ile Glu Glu Ile His SerVal Ser Ala Lys Asn 945 950 955 960 Arg Ala Val Ser Ile Glu Lys Ala GluLys Lys Trp Glu Glu Lys Arg 965 970 975 Gln Asn Leu Asp His Tyr Asn GlyLys Glu Phe Glu Lys Leu Leu Glu 980 985 990 Glu Ala Gln Ala Asn Ile MetLys Ser Ile Pro Asn Leu Glu Met Pro 995 1000 1005 Pro Ala Thr Gly ProLeu Pro Arg Gly Asp Ala Pro Val Asp Lys 1010 1015 1020 Val Glu Leu SerGlu Asp Ser Pro Asn Ser Glu Gln Asp Leu Glu 1025 1030 1035 Lys Leu GlyGly Lys Ser Pro Pro Pro Pro Pro Pro Pro Pro Arg 1040 1045 1050 Arg SerTyr Leu Pro Gly Ser Gly Leu Thr Thr Thr Arg Ser Gly 1055 1060 1065 AspVal Val Tyr Thr Gly Arg Lys Glu Asn Ile Thr Ala Lys Ala 1070 1075 1080Ser Ser Glu Asp Ala Gly Pro Ser Pro Gln Thr Arg Ala Thr Lys 1085 10901095 Tyr Pro Ala Glu Glu Pro Ala Ser Ala Trp Thr Pro Ser Pro Pro 11001105 1110 Pro Val Thr Thr Ser Ser Ser Lys Asp Glu Glu Glu Glu Glu Glu1115 1120 1125 Glu Gly Asp Lys Ile Met Ala Glu Leu Gln Ala Phe Gln LysCys 1130 1135 1140 Ser Phe Met Asp Val Asn Ser Asn Ser His Ala Glu ProSer Arg 1145 1150 1155 Ala Asp Ser His Val Lys Asp Thr Arg Ser Gly AlaThr Val Pro 1160 1165 1170 Pro Lys Glu Lys Lys Asn Leu Glu Phe Phe HisGlu Asp Val Arg 1175 1180 1185 Lys Ser Asp Val Glu Tyr Glu Asn Gly ProGln Met Glu Phe Gln 1190 1195 1200 Lys Val Thr Thr Gly Ala Val Arg ProSer Asp Pro Pro Lys Trp 1205 1210 1215 Glu Arg Gly Met Glu Asn Ser IleSer Asp Ala Ser Arg Thr Ser 1220 1225 1230 Glu Tyr Lys Thr Glu Ile IleMet Lys Glu Asn Ser Ile Ser Asn 1235 1240 1245 Met Ser Leu Leu Arg AspSer Arg Asn Tyr Ser Gln Glu Thr Val 1250 1255 1260 Pro Lys Ala Ser PheGly Phe Ser Gly Ile Ser Pro Leu Glu Asp 1265 1270 1275 Glu Ile Asn LysGly Ser Lys Ile Ser Gly Leu Gln Tyr Ser Ile 1280 1285 1290 Pro Asp ThrGlu Asn Gln Thr Leu Asn Tyr Gly Lys Thr Lys Glu 1295 1300 1305 Met GluLys Gln Asn Thr Asp Lys Cys His Val Ser Ser His Thr 1310 1315 1320 ArgLeu Thr Glu Ser Ser Val His Asp Phe Lys Thr Glu Asp Gln 1325 1330 1335Glu Val Ile Thr Thr Asp Phe Gly Gln Val Val Leu Arg Pro Lys 1340 13451350 Glu Ala Arg His Ala Asn Val Asn Pro Asn Glu Asp Gly Glu Ser 13551360 1365 Ser Ser Ser Ser Pro Thr Glu Glu Asn Ala Ala Thr Asp Asn Ile1370 1375 1380 Ala Phe Met Ile Thr Glu Thr Thr Val Gln Val Leu Ser SerGly 1385 1390 1395 Glu Val His Asp Ile Val Ser Gln Lys Gly Glu Asp IleGln Thr 1400 1405 1410 Val Asn Ile Asp Ala Arg Lys Glu Met Thr Pro ArgGln Glu Gly 1415 1420 1425 Thr Asp Asn Glu Asp Pro Val Val Cys Leu AspLys Lys Pro Val 1430 1435 1440 Ile Ile Ile Phe Asp Glu Pro Met Asp IleArg Ser Ala Tyr Lys 1445 1450 1455 Arg Leu Ser Thr Ile Phe Glu Glu CysAsp Glu Glu Leu Glu Arg 1460 1465 1470 Met Met Met Glu Glu Lys Ile GluGlu Glu Glu Glu Glu Glu Asn 1475 1480 1485 Gly Asp Ser Val Val Gln AsnAsn Asn Thr Ser Gln Met Ser His 1490 1495 1500 Lys Lys Val Ala Pro GlyAsn Leu Arg Thr Gly Gln Gln Val Glu 1505 1510 1515 Thr Lys Ser Gln ProHis Ser Leu Ala Thr Glu Thr Arg Asn Pro 1520 1525 1530 Gly Gly Gln GluMet Asn Arg Thr Glu Leu Asn Lys Phe Ser His 1535 1540 1545 Val Asp SerPro Asn Ser Glu Cys Lys Gly Glu Asp Ala Thr Asp 1550 1555 1560 Asp GlnPhe Glu Ser Pro Lys Lys Lys Phe Lys Phe Lys Phe Pro 1565 1570 1575 LysLys Gln Leu Ala Ala Leu Thr Gln Ala Ile Arg Thr Gly Thr 1580 1585 1590Lys Thr Gly Lys Lys Thr Leu Gln Val Val Val Tyr Glu Glu Glu 1595 16001605 Glu Glu Asp Gly Thr Leu Lys Gln His Lys Glu Ala Lys Arg Phe 16101615 1620 Glu Ile Ala Arg Ser Gln Pro Glu Asp Thr Pro Glu Asn Thr Val1625 1630 1635 Arg Arg Gln Glu Gln Pro Ser Ile Glu Ser Thr Ser Pro IleSer 1640 1645 1650 Arg Thr Asp Glu Ile Arg Lys Asn Thr Tyr Arg Thr LeuAsp Ser 1655 1660 1665 Leu Glu Gln Thr Ile Lys Gln Leu Glu Asn Thr IleSer Glu Met 1670 1675 1680 Ser Pro Lys Ala Leu Val Asp Thr Ser Cys SerSer Asn Arg Asp 1685 1690 1695 Ser Val Ala Ser Ser Ser His Ile Ala GlnGlu Ala Ser Pro Arg 1700 1705 1710 Pro Leu Leu Val Pro Asp Glu Gly ProThr Ala Leu Glu Pro Pro 1715 1720 1725 Thr Ser Ile Pro Ser Ala Ser ArgLys Val Ser Trp Ser Ala Gly 1730 1735 1740 Lys 12 8362 DNA Homo sapiensCDS (1)..(5127) 12 atg gaa gaa aat gaa agc cag aaa tgt gag ccg tgc cttcct tac tca 48 Met Glu Glu Asn Glu Ser Gln Lys Cys Glu Pro Cys Leu ProTyr Ser 1 5 10 15 gca gac aga aga cag atg cag gaa caa ggc aaa ggc aatctg cat gta 96 Ala Asp Arg Arg Gln Met Gln Glu Gln Gly Lys Gly Asn LeuHis Val 20 25 30 aca tca cca gaa gat gca gaa tgc cgc aga acc aag gaa cgcctt tct 144 Thr Ser Pro Glu Asp Ala Glu Cys Arg Arg Thr Lys Glu Arg LeuSer 35 40 45 aat gga aac agt cgt ggt tca gtt tcc aag tct tcc cgc aat atccca 192 Asn Gly Asn Ser Arg Gly Ser Val Ser Lys Ser Ser Arg Asn Ile Pro50 55 60 agg aga cac acc cta ggg ggg ccc cga agt tcc aag gaa ata ctg gga240 Arg Arg His Thr Leu Gly Gly Pro Arg Ser Ser Lys Glu Ile Leu Gly 6570 75 80 atg caa aca tct gag atg gat cgg aag aga gaa gcg ttc cta gaa cat288 Met Gln Thr Ser Glu Met Asp Arg Lys Arg Glu Ala Phe Leu Glu His 8590 95 ctg aag cag aag tac ccc cac cac gcc tct gca atc atg ggt cac caa336 Leu Lys Gln Lys Tyr Pro His His Ala Ser Ala Ile Met Gly His Gln 100105 110 gag agg ctg aga gac cag aca agg agc ccc aaa ctg tct cac agt cct384 Glu Arg Leu Arg Asp Gln Thr Arg Ser Pro Lys Leu Ser His Ser Pro 115120 125 caa cca ccc agt ctg ggt gac ccg gtc gag cat tta tca gag acg tcc432 Gln Pro Pro Ser Leu Gly Asp Pro Val Glu His Leu Ser Glu Thr Ser 130135 140 gct gat tct ttg gaa gcc atg tct gag ggg gat gct cca acc cct ttt480 Ala Asp Ser Leu Glu Ala Met Ser Glu Gly Asp Ala Pro Thr Pro Phe 145150 155 160 tcc aga ggc agc cgg act cgt gcg agc ctt cct gtg gtg agg tcaacc 528 Ser Arg Gly Ser Arg Thr Arg Ala Ser Leu Pro Val Val Arg Ser Thr165 170 175 aac cag acg aaa gaa aga tct ctg ggg gtt ctc tat ctc cag tatgga 576 Asn Gln Thr Lys Glu Arg Ser Leu Gly Val Leu Tyr Leu Gln Tyr Gly180 185 190 gat gaa acc aag cag ctc agg atg ccg aat gaa atc aca agt gcagac 624 Asp Glu Thr Lys Gln Leu Arg Met Pro Asn Glu Ile Thr Ser Ala Asp195 200 205 aca atc cgt gct ctc ttc gta agt gcc ttt cca cag cag ctc accatg 672 Thr Ile Arg Ala Leu Phe Val Ser Ala Phe Pro Gln Gln Leu Thr Met210 215 220 aaa atg ctg gaa tcg ccc agt gtc gcc att tac atc aaa gat gaaagc 720 Lys Met Leu Glu Ser Pro Ser Val Ala Ile Tyr Ile Lys Asp Glu Ser225 230 235 240 aga aat gtc tat tat gaa tta aat gat gta agg aac att caagac aga 768 Arg Asn Val Tyr Tyr Glu Leu Asn Asp Val Arg Asn Ile Gln AspArg 245 250 255 tca ctc ctc aaa gtg tac aac aag gat cct gca cat gcg tttaat cac 816 Ser Leu Leu Lys Val Tyr Asn Lys Asp Pro Ala His Ala Phe AsnHis 260 265 270 aca cca aaa act atg aat gga gac atg agg atg cag aga gaactt gtt 864 Thr Pro Lys Thr Met Asn Gly Asp Met Arg Met Gln Arg Glu LeuVal 275 280 285 tat gca aga gga gat ggc cct ggg gcc cct cgc ccc gga tctact gct 912 Tyr Ala Arg Gly Asp Gly Pro Gly Ala Pro Arg Pro Gly Ser ThrAla 290 295 300 cat cca ccc cat gcg att cca aat tcc cca ccg tct act ccagtg ccc 960 His Pro Pro His Ala Ile Pro Asn Ser Pro Pro Ser Thr Pro ValPro 305 310 315 320 cat tcc atg ccc ccc tcc ccg tcc aga att cct tat gggggc acc cgc 1008 His Ser Met Pro Pro Ser Pro Ser Arg Ile Pro Tyr Gly GlyThr Arg 325 330 335 tcc atg gtt gtt cct ggc aat gcc acc atc ccc agg gacaga atc tcc 1056 Ser Met Val Val Pro Gly Asn Ala Thr Ile Pro Arg Asp ArgIle Ser 340 345 350 agc ctg cca gtc tcc aga ccc atc tct cca agc cca agcgcc att tta 1104 Ser Leu Pro Val Ser Arg Pro Ile Ser Pro Ser Pro Ser AlaIle Leu 355 360 365 gaa aga aga gat gtc aag cct gat gaa gac atg agt ggcaaa aac att 1152 Glu Arg Arg Asp Val Lys Pro Asp Glu Asp Met Ser Gly LysAsn Ile 370 375 380 gca atg tac aga aat gag ggt ttc tat gct gat cct tacctt tat cac 1200 Ala Met Tyr Arg Asn Glu Gly Phe Tyr Ala Asp Pro Tyr LeuTyr His 385 390 395 400 gag gga cgg atg agc ata gcc tca tcc cat ggt ggacac cca ctg gat 1248 Glu Gly Arg Met Ser Ile Ala Ser Ser His Gly Gly HisPro Leu Asp 405 410 415 gtc ccc gac cac atc att gca tat cac cgc acc gccatc cgg tca gcg 1296 Val Pro Asp His Ile Ile Ala Tyr His Arg Thr Ala IleArg Ser Ala 420 425 430 agt gct tat tgt aac ccc tca atg caa gcg gaa atgcat atg gaa caa 1344 Ser Ala Tyr Cys Asn Pro Ser Met Gln Ala Glu Met HisMet Glu Gln 435 440 445 tca ctg tac aga cag aaa tca agg aaa tat ccg gatagc cat ttg cct 1392 Ser Leu Tyr Arg Gln Lys Ser Arg Lys Tyr Pro Asp SerHis Leu Pro 450 455 460 aca ctg ggc tcc aaa aca ccc cct gcc tct cct cacaga gtc agt gac 1440 Thr Leu Gly Ser Lys Thr Pro Pro Ala Ser Pro His ArgVal Ser Asp 465 470 475 480 ctg agg atg ata gac atg cac gct cac tat aatgcc cac ggc ccc cct 1488 Leu Arg Met Ile Asp Met His Ala His Tyr Asn AlaHis Gly Pro Pro 485 490 495 cac acc atg cag cca gac cgg gcc tct ccg agccgc cag gcc ttt aaa 1536 His Thr Met Gln Pro Asp Arg Ala Ser Pro Ser ArgGln Ala Phe Lys 500 505 510 aag gag cca ggc acc ttg gtg tat ata gaa aagcca cgg agc gct gca 1584 Lys Glu Pro Gly Thr Leu Val Tyr Ile Glu Lys ProArg Ser Ala Ala 515 520 525 gga tta tcc agc ctt gta gac ctc ggc cct cctcta atg gag aag caa 1632 Gly Leu Ser Ser Leu Val Asp Leu Gly Pro Pro LeuMet Glu Lys Gln 530 535 540 gtt ttt gcc tac agc acg gcg aca ata ccc aaagac aga gag acc agc 1680 Val Phe Ala Tyr Ser Thr Ala Thr Ile Pro Lys AspArg Glu Thr Ser 545 550 555 560 gag aaa atg atg aaa acc aca gcc aac aggaac cac aca gat agt gca 1728 Glu Lys Met Met Lys Thr Thr Ala Asn Arg AsnHis Thr Asp Ser Ala 565 570 575 gga acg ccc cat gtg tct ggt ggg aag atgctc agt gct ctg gag tcc 1776 Gly Thr Pro His Val Ser Gly Gly Lys Met LeuSer Ala Leu Glu Ser 580 585 590 acg gtg cct ccc agc cag cct cca cct gtgggc acc tca gcc atc cac 1824 Thr Val Pro Pro Ser Gln Pro Pro Pro Val GlyThr Ser Ala Ile His 595 600 605 atg agc ctg ctt gag atg agg cgg agc gtggcg gaa ctc agg ctc cag 1872 Met Ser Leu Leu Glu Met Arg Arg Ser Val AlaGlu Leu Arg Leu Gln 610 615 620 ctc cag cag atg cgg cag ctc cag ctg cagaac cag gag ttg ctg agg 1920 Leu Gln Gln Met Arg Gln Leu Gln Leu Gln AsnGln Glu Leu Leu Arg 625 630 635 640 gca atg atg aag aag gcc gag ctg gaaatc agt ggc aaa gtg atg gaa 1968 Ala Met Met Lys Lys Ala Glu Leu Glu IleSer Gly Lys Val Met Glu 645 650 655 aca atg aag aga ctg gag gat ccc gtgcag cga cag cgc gtc cta gtg 2016 Thr Met Lys Arg Leu Glu Asp Pro Val GlnArg Gln Arg Val Leu Val 660 665 670 gag caa gag aga caa aaa tat ctt catgag gaa gag aag atc gtc aag 2064 Glu Gln Glu Arg Gln Lys Tyr Leu His GluGlu Glu Lys Ile Val Lys 675 680 685 aag ttg tgc gag ttg gaa gac ttt gttgaa gac ttg aag aag gac tcc 2112 Lys Leu Cys Glu Leu Glu Asp Phe Val GluAsp Leu Lys Lys Asp Ser 690 695 700 acg gca gcc agc cga ttg gtt act ctgaaa gac gtg gaa gac ggg gct 2160 Thr Ala Ala Ser Arg Leu Val Thr Leu LysAsp Val Glu Asp Gly Ala 705 710 715 720 ttc ctc ctg cgt caa gtg gga gaggct gta gct acc ctg aaa gga gaa 2208 Phe Leu Leu Arg Gln Val Gly Glu AlaVal Ala Thr Leu Lys Gly Glu 725 730 735 ttt cca acc tta caa aac aag atgcga gcc atc ctg cgc ata gaa gtg 2256 Phe Pro Thr Leu Gln Asn Lys Met ArgAla Ile Leu Arg Ile Glu Val 740 745 750 gag gcc gtg cgg ttt ctg aag gaggag cca cac aag ctg gac agt ctc 2304 Glu Ala Val Arg Phe Leu Lys Glu GluPro His Lys Leu Asp Ser Leu 755 760 765 ctg aag cgt gtg cgc agc atg acagac gtc ctg acc atg ctg cgg aga 2352 Leu Lys Arg Val Arg Ser Met Thr AspVal Leu Thr Met Leu Arg Arg 770 775 780 cat gtc act gat ggg ctc ctg aaaggc acg gac gca gcc caa gcc gca 2400 His Val Thr Asp Gly Leu Leu Lys GlyThr Asp Ala Ala Gln Ala Ala 785 790 795 800 cag tac atg gct atg gaa aaggcc aca gcc gca gaa gtc ctg aag agt 2448 Gln Tyr Met Ala Met Glu Lys AlaThr Ala Ala Glu Val Leu Lys Ser 805 810 815 cag gag gag gca gcc cac acctcc ggc cag ccc ttc cac agc aca ggt 2496 Gln Glu Glu Ala Ala His Thr SerGly Gln Pro Phe His Ser Thr Gly 820 825 830 gcc cct ggc gat gcg aag tcggaa gtg gtg cct ttg tcc ggc atg atg 2544 Ala Pro Gly Asp Ala Lys Ser GluVal Val Pro Leu Ser Gly Met Met 835 840 845 gtt cgc cac gcg cag agc tcccct gtg gtc atc cag ccc tcc cag cac 2592 Val Arg His Ala Gln Ser Ser ProVal Val Ile Gln Pro Ser Gln His 850 855 860 tcc gtg gcc ctg ctg aac cctgct cag aac ttg cct cac gtg gcc agc 2640 Ser Val Ala Leu Leu Asn Pro AlaGln Asn Leu Pro His Val Ala Ser 865 870 875 880 tcc cca gcc gtc ccc caggaa gca acc tcc act ctg cag atg tcg cag 2688 Ser Pro Ala Val Pro Gln GluAla Thr Ser Thr Leu Gln Met Ser Gln 885 890 895 gct ccg cag tcc cca cagata ccc atg aat ggg tct gcc atg cag agc 2736 Ala Pro Gln Ser Pro Gln IlePro Met Asn Gly Ser Ala Met Gln Ser 900 905 910 ttg ttc att gaa gaa atccac agt gtg agt gcc aag aac agg gca gtg 2784 Leu Phe Ile Glu Glu Ile HisSer Val Ser Ala Lys Asn Arg Ala Val 915 920 925 tct atc gag aaa gca gaaaag aaa tgg gag gaa aaa agg caa aat ctg 2832 Ser Ile Glu Lys Ala Glu LysLys Trp Glu Glu Lys Arg Gln Asn Leu 930 935 940 gat cac tat aat ggg aaagag ttt gag aag ctc cta gaa gaa gct cag 2880 Asp His Tyr Asn Gly Lys GluPhe Glu Lys Leu Leu Glu Glu Ala Gln 945 950 955 960 gcc aat atc atg aagtca ata cca aat ctg gag atg ccg cca gcc aca 2928 Ala Asn Ile Met Lys SerIle Pro Asn Leu Glu Met Pro Pro Ala Thr 965 970 975 ggc cca ctg cca agggga gat gcc cca gtg gac aag gtg gaa ctt tca 2976 Gly Pro Leu Pro Arg GlyAsp Ala Pro Val Asp Lys Val Glu Leu Ser 980 985 990 gaa gat tct cca aattcg gaa cag gac ttg gaa aag ctg ggg gga aag 3024 Glu Asp Ser Pro Asn SerGlu Gln Asp Leu Glu Lys Leu Gly Gly Lys 995 1000 1005 tcg ccc cct cctcct ccg cca cct cct cgt cga agc tac ctg cca 3069 Ser Pro Pro Pro Pro ProPro Pro Pro Arg Arg Ser Tyr Leu Pro 1010 1015 1020 gga tcg gga ctc accacc acg agg tca ggc gat gtg gtc tac acc 3114 Gly Ser Gly Leu Thr Thr ThrArg Ser Gly Asp Val Val Tyr Thr 1025 1030 1035 ggc aga aag gag aac atcacc gct aag gca agc agt gaa gat gct 3159 Gly Arg Lys Glu Asn Ile Thr AlaLys Ala Ser Ser Glu Asp Ala 1040 1045 1050 gga cca agc cca cag acc agagct aca aaa tat cca gca gag gag 3204 Gly Pro Ser Pro Gln Thr Arg Ala ThrLys Tyr Pro Ala Glu Glu 1055 1060 1065 cct gct tca gcc tgg acc cca tcccca ccg cct gtc acc acc tcc 3249 Pro Ala Ser Ala Trp Thr Pro Ser Pro ProPro Val Thr Thr Ser 1070 1075 1080 tcc tca aag gat gag gag gaa gaa gaagaa gaa gga gac aaa ata 3294 Ser Ser Lys Asp Glu Glu Glu Glu Glu Glu GluGly Asp Lys Ile 1085 1090 1095 atg gca gaa ctc cag gca ttc cag aag tgttcc ttt atg gat gta 3339 Met Ala Glu Leu Gln Ala Phe Gln Lys Cys Ser PheMet Asp Val 1100 1105 1110 aat tca aac agt cat gct gag cca tcc cgg gctgac agt cac gtt 3384 Asn Ser Asn Ser His Ala Glu Pro Ser Arg Ala Asp SerHis Val 1115 1120 1125 aaa gac act agg tcg ggc gcc aca gtg cca ccc aaggag aag aag 3429 Lys Asp Thr Arg Ser Gly Ala Thr Val Pro Pro Lys Glu LysLys 1130 1135 1140 aat ttg gaa ttt ttc cat gaa gat gta cgg aaa tct gatgtt gaa 3474 Asn Leu Glu Phe Phe His Glu Asp Val Arg Lys Ser Asp Val Glu1145 1150 1155 tat gaa aat ggc ccc caa atg gaa ttc caa aag gtt acc acaggg 3519 Tyr Glu Asn Gly Pro Gln Met Glu Phe Gln Lys Val Thr Thr Gly1160 1165 1170 gct gta aga cct agt gac cct cct aag tgg gaa aga gga atggag 3564 Ala Val Arg Pro Ser Asp Pro Pro Lys Trp Glu Arg Gly Met Glu1175 1180 1185 aat agt att tct gat gca tca aga aca tca gaa tat aaa actgag 3609 Asn Ser Ile Ser Asp Ala Ser Arg Thr Ser Glu Tyr Lys Thr Glu1190 1195 1200 atc ata atg aag gaa aat tcc ata tcc aat atg agt tta ctcaga 3654 Ile Ile Met Lys Glu Asn Ser Ile Ser Asn Met Ser Leu Leu Arg1205 1210 1215 gac agt aga aac tat tcc cag gaa act gtg cct aag gcc agtttc 3699 Asp Ser Arg Asn Tyr Ser Gln Glu Thr Val Pro Lys Ala Ser Phe1220 1225 1230 ggt ttc tct ggc att agt cca tta gaa gat gaa ata aac aaaggg 3744 Gly Phe Ser Gly Ile Ser Pro Leu Glu Asp Glu Ile Asn Lys Gly1235 1240 1245 tct aaa atc tca ggc ctg caa tac tct ata cct gac acc gagaac 3789 Ser Lys Ile Ser Gly Leu Gln Tyr Ser Ile Pro Asp Thr Glu Asn1250 1255 1260 cag acg ctg aat tac gga aag aca aag gag atg gaa aag caaaat 3834 Gln Thr Leu Asn Tyr Gly Lys Thr Lys Glu Met Glu Lys Gln Asn1265 1270 1275 acg gat aag tgt cac gtt tcc tct cac act aga cta aca gaatca 3879 Thr Asp Lys Cys His Val Ser Ser His Thr Arg Leu Thr Glu Ser1280 1285 1290 agc gtg cat gat ttt aaa aca gaa gat caa gag gtt atc acgaca 3924 Ser Val His Asp Phe Lys Thr Glu Asp Gln Glu Val Ile Thr Thr1295 1300 1305 gat ttt ggc caa gtt gtt cta aga ccc aag gag gca agg catgct 3969 Asp Phe Gly Gln Val Val Leu Arg Pro Lys Glu Ala Arg His Ala1310 1315 1320 aac gtg aac cct aat gag gat gga gaa tca agt tca agt tctccc 4014 Asn Val Asn Pro Asn Glu Asp Gly Glu Ser Ser Ser Ser Ser Pro1325 1330 1335 act gaa gaa aat gca gcc act gac aat att gcc ttc atg attacc 4059 Thr Glu Glu Asn Ala Ala Thr Asp Asn Ile Ala Phe Met Ile Thr1340 1345 1350 gaa acc act gtc cag gtt ctt tcc agt ggg gag gtg cat gatatt 4104 Glu Thr Thr Val Gln Val Leu Ser Ser Gly Glu Val His Asp Ile1355 1360 1365 gtt agc caa aag gga gaa gac ata cag acg gtt aat atc gatgcc 4149 Val Ser Gln Lys Gly Glu Asp Ile Gln Thr Val Asn Ile Asp Ala1370 1375 1380 aga aaa gag atg acc ccc cga caa gaa ggg act gac aat gaggat 4194 Arg Lys Glu Met Thr Pro Arg Gln Glu Gly Thr Asp Asn Glu Asp1385 1390 1395 cca gtc gtg tgc ctg gac aag aaa cca gtg atc atc att ttcgat 4239 Pro Val Val Cys Leu Asp Lys Lys Pro Val Ile Ile Ile Phe Asp1400 1405 1410 gag ccc atg gac atc cgg tct gcc tat aag aga ctt tca actatc 4284 Glu Pro Met Asp Ile Arg Ser Ala Tyr Lys Arg Leu Ser Thr Ile1415 1420 1425 ttt gag gaa tgt gat gag gaa tta gag aga atg atg atg gaggaa 4329 Phe Glu Glu Cys Asp Glu Glu Leu Glu Arg Met Met Met Glu Glu1430 1435 1440 aag ata gag gag gag gaa gag gag gaa aat ggg gat tct gtagtc 4374 Lys Ile Glu Glu Glu Glu Glu Glu Glu Asn Gly Asp Ser Val Val1445 1450 1455 cag aat aat aac act tcc cag atg tct cat aag aag gtg gcccca 4419 Gln Asn Asn Asn Thr Ser Gln Met Ser His Lys Lys Val Ala Pro1460 1465 1470 ggc aat ctt aga acc gga caa cag gtg gaa aca aag tca cagcca 4464 Gly Asn Leu Arg Thr Gly Gln Gln Val Glu Thr Lys Ser Gln Pro1475 1480 1485 cac tcc ctg gcc aca gag acc aga aac cca gga gga cag gaaatg 4509 His Ser Leu Ala Thr Glu Thr Arg Asn Pro Gly Gly Gln Glu Met1490 1495 1500 aac aga acg gag ctg aac aag ttc agc cac gtg gat tct ccaaat 4554 Asn Arg Thr Glu Leu Asn Lys Phe Ser His Val Asp Ser Pro Asn1505 1510 1515 tcg gaa tgc aag ggt gag gac gcg acc gat gac cag ttt gaaagc 4599 Ser Glu Cys Lys Gly Glu Asp Ala Thr Asp Asp Gln Phe Glu Ser1520 1525 1530 ccc aag aaa aag ttt aaa ttc aaa ttc cct aag aag caa ctcgcc 4644 Pro Lys Lys Lys Phe Lys Phe Lys Phe Pro Lys Lys Gln Leu Ala1535 1540 1545 gct ctc act caa gcc att cgc acc gga act aaa aca ggg aagaag 4689 Ala Leu Thr Gln Ala Ile Arg Thr Gly Thr Lys Thr Gly Lys Lys1550 1555 1560 act ttg caa gtg gta gtc tat gaa gaa gag gaa gag gat ggcacc 4734 Thr Leu Gln Val Val Val Tyr Glu Glu Glu Glu Glu Asp Gly Thr1565 1570 1575 ctg aaa cag cac aaa gaa gcc aag cgc ttc gaa atc gct aggtct 4779 Leu Lys Gln His Lys Glu Ala Lys Arg Phe Glu Ile Ala Arg Ser1580 1585 1590 caa cct gaa gac acc cct gaa aac aca gtg agg agg caa gagcag 4824 Gln Pro Glu Asp Thr Pro Glu Asn Thr Val Arg Arg Gln Glu Gln1595 1600 1605 ccc agc atc gag agt aca tct ccg att tca aga act gat gaaatt 4869 Pro Ser Ile Glu Ser Thr Ser Pro Ile Ser Arg Thr Asp Glu Ile1610 1615 1620 aga aaa aac acc tac aga aca ttg gat agc ctg gag cag accatt 4914 Arg Lys Asn Thr Tyr Arg Thr Leu Asp Ser Leu Glu Gln Thr Ile1625 1630 1635 aaa cag ctc gaa aat aca atc agt gaa atg agt ccc aaa gcccta 4959 Lys Gln Leu Glu Asn Thr Ile Ser Glu Met Ser Pro Lys Ala Leu1640 1645 1650 gtt gat acc tca tgt tct tcc aac aga gat tct gtt gca agttca 5004 Val Asp Thr Ser Cys Ser Ser Asn Arg Asp Ser Val Ala Ser Ser1655 1660 1665 tcc cac ata gcc caa gag gcc tct ccc cga ccc ttg cta gttccg 5049 Ser His Ile Ala Gln Glu Ala Ser Pro Arg Pro Leu Leu Val Pro1670 1675 1680 gat gaa ggt ccc act gcc cta gag ccc cct acg tcg ata ccttca 5094 Asp Glu Gly Pro Thr Ala Leu Glu Pro Pro Thr Ser Ile Pro Ser1685 1690 1695 gct tca cgt aag gta tct tgg tct gct gga aaa tgaaaagacc5137 Ala Ser Arg Lys Val Ser Trp Ser Ala Gly Lys 1700 1705 cagctgctttcctaaatctg ccataatcac cattagtgaa aggtgtcttg taacttaatt 5197 gctttctttcaggtggcttt tttttttttg tctgttcgcc atgaaaccct tctttcatac 5257 tttctccctcaccttccaaa caacaacaac taggtatcta acagctaatc agttctgttt 5317 ttgcctctgttgctgactgg tgttgggtaa acacgaggct gctgggtcag ccatgtgctg 5377 ttgaaatggttgctctgata ctcacattaa aatccgtttg atcagtagtg agcagttgat 5437 tctgtttgattcttctgatt aaccccagtt ggtgtctcct agatctgtcc tgcatgtagg 5497 gctgtggcttctcaccttga gcttctctgc acatcgtggg gcagcctcac agatgaccta 5557 ctcatgcgcttctccttctc ttccccctct cactggtcct tcccacaggg ctccagcggg 5617 gccccacagacgagcaggat gcctgtcccc atgagtgcca agaacagacc cggaaccctg 5677 gacaaacccggcaagcagtc caaactgcag gatccccgcc aatatcgtca ggtagtttta 5737 ccttaaacccacttttggat ggacgctatt tcagttaagc aagtcactga cttagtttat 5797 accaaatattgtgctttctt tgtaagataa cggtttacat agacatcctg gatctggggg 5857 catgaagaaagtctaaataa acctttgtta cactttttta ccacgctttt gcatgcttgc 5917 aataaaacatcttttacttt gtgactccaa actccaaatt ttaactgtta acacacggtg 5977 ccagaccaggtggcttttct ttggtgaatg tagtgtttca tctgaacacc tcgggaagca 6037 gagacaaaccaacctgtggt tgaactgccc ttaacgtcac cactactaac gtctatgttg 6097 actgtattgtgttagaagca cattaacact ccgtcacaat gcccgacccc caccccagta 6157 attatccagacgcatggccc acctggcaca caggaaatgg tagagctgga atgatgggac 6217 tcctctcacaaatgtattct tcctttcctc ctttcccgtc catcctttgc tatgtacatg 6277 gggggtttctaccaggtcca gtagagcaca acaagactta gctcaggcct tgaactgtgt 6337 ttggttggttttctttgatt gaattattct cagaagggct gtgttgccag gccctgtggg 6397 ttgatcatgtgaccgccttt ctgacaaaat gtctcccgcc atctttattt gcaggctaat 6457 ggaagtgctaagaaatctgg tggggacttt aagcctactt ccccctcctt acctgcttct 6517 aagattccagccctttctcc cagctctggg aaaagcagtt ctctgccctc ttctagtggt 6577 gacagctctaacctccctaa tccacctgct actaaaccat cgattgcttc taaccctctc 6637 agcccccaaacaggaccacc tgctcactct gcctccctca tcccttctgt ctctaatggc 6697 tctttgaagtttcagagcct cactcataca ggtaaaggtc accatctttc attctcaccg 6757 cagagtcaaaatggccgagc accccctcct ttgtcatttt cctcctcccc tccttctcct 6817 gcctcctccgtctcactgaa tcaaggtgcc aagggcacca ggaccatcca tactcccagc 6877 ctcaccagctacaaggcaca gaatggaagt tcaagcaaag ccaccccatc cacagcaaaa 6937 gaaacctcttaaaggtcaaa tcctattagg cacaagtcgg agttacattt aaaaaaaatt 6997 aacagtctacaacaactgtt ttcacaagag aatgtaacat attgctgtat cgtttgaggc 7057 ttaatgctaaatatgtgcta aatactggat taatagattt cagtaaagct cgttcgtttt 7117 gtttggttttctttttacct agttgctata gtgtctacag tctatactca atacctataa 7177 aatgcagtaagcatgtgtta cagaaagagg ttctggtggg agagaaaggt gcgtgtgaga 7237 caggagaattgtcttaagca tataaaacat gtatgattcc agaattttag tatgttttgt 7297 ataaaactatttttcattac ggagactaga agtgaacaga gaattacaca agtgtgacta 7357 tacaaattgtaaaacagata ctataatatt tccttttatt ttagtgttat ttagctttat 7417 tacagatttctatttttgtc aaaacttcat ggttcctttc aagatctttt ttgccaaaac 7477 attttgatactatagcattg tacatttgaa agtagtgttc tagactataa aaccaatgaa 7537 cttctacatgagccctacag acaggcatgt gtagaaggca atttatcaaa cctattgcac 7597 tgccatgaaaagtgtgtata ataatttgct agcccaagca agctagtttt ctttgcttgc 7657 ttcttttctttcttttttcc ttcctttttt tttttttttt cttttttaac atgttgagat 7717 tctctagttgttttctttgg cgtatctaac cccttctttt gttttctgag acctggtaac 7777 ccacgctcttgcattgtgga ttttaaaatg tatactctgt acggttctgt aaaccgaaaa 7837 acttttgtaaatatataaat atacatagac ataaaaatac tgtatgtgac agcacataga 7897 gtagttttcccacaccaaag ttaattttta tgcatgcttt aaaagtatat atcgggaccg 7957 gcagaaatggaagtatccat acatttttaa aaagcaacaa gtttgcacag ctagagtgtt 8017 tttgtaaataaatgtatttg tataacacag tcatgtaata tacagaacta taagcagaga 8077 ctttgcaaaactaaataaag ggctgcatgc ttattatttt ttgtaccttg tcactataac 8137 tacttcctagtcaaagaacg aaatgtaact gttaccgagt taaatgtttt tccgctttga 8197 gggatgtaaccacatccact cagaggacac tacttttctg aaagctctgg ggtgactaat 8257 gatgagttcctaataaatta attgcaagtg tggtgccttg gaaaaaaaaa aaaaaaaaaa 8317 aaaaaaaaaaaaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa 8362 13 1709 PRT Homo sapiens 13Met Glu Glu Asn Glu Ser Gln Lys Cys Glu Pro Cys Leu Pro Tyr Ser 1 5 1015 Ala Asp Arg Arg Gln Met Gln Glu Gln Gly Lys Gly Asn Leu His Val 20 2530 Thr Ser Pro Glu Asp Ala Glu Cys Arg Arg Thr Lys Glu Arg Leu Ser 35 4045 Asn Gly Asn Ser Arg Gly Ser Val Ser Lys Ser Ser Arg Asn Ile Pro 50 5560 Arg Arg His Thr Leu Gly Gly Pro Arg Ser Ser Lys Glu Ile Leu Gly 65 7075 80 Met Gln Thr Ser Glu Met Asp Arg Lys Arg Glu Ala Phe Leu Glu His 8590 95 Leu Lys Gln Lys Tyr Pro His His Ala Ser Ala Ile Met Gly His Gln100 105 110 Glu Arg Leu Arg Asp Gln Thr Arg Ser Pro Lys Leu Ser His SerPro 115 120 125 Gln Pro Pro Ser Leu Gly Asp Pro Val Glu His Leu Ser GluThr Ser 130 135 140 Ala Asp Ser Leu Glu Ala Met Ser Glu Gly Asp Ala ProThr Pro Phe 145 150 155 160 Ser Arg Gly Ser Arg Thr Arg Ala Ser Leu ProVal Val Arg Ser Thr 165 170 175 Asn Gln Thr Lys Glu Arg Ser Leu Gly ValLeu Tyr Leu Gln Tyr Gly 180 185 190 Asp Glu Thr Lys Gln Leu Arg Met ProAsn Glu Ile Thr Ser Ala Asp 195 200 205 Thr Ile Arg Ala Leu Phe Val SerAla Phe Pro Gln Gln Leu Thr Met 210 215 220 Lys Met Leu Glu Ser Pro SerVal Ala Ile Tyr Ile Lys Asp Glu Ser 225 230 235 240 Arg Asn Val Tyr TyrGlu Leu Asn Asp Val Arg Asn Ile Gln Asp Arg 245 250 255 Ser Leu Leu LysVal Tyr Asn Lys Asp Pro Ala His Ala Phe Asn His 260 265 270 Thr Pro LysThr Met Asn Gly Asp Met Arg Met Gln Arg Glu Leu Val 275 280 285 Tyr AlaArg Gly Asp Gly Pro Gly Ala Pro Arg Pro Gly Ser Thr Ala 290 295 300 HisPro Pro His Ala Ile Pro Asn Ser Pro Pro Ser Thr Pro Val Pro 305 310 315320 His Ser Met Pro Pro Ser Pro Ser Arg Ile Pro Tyr Gly Gly Thr Arg 325330 335 Ser Met Val Val Pro Gly Asn Ala Thr Ile Pro Arg Asp Arg Ile Ser340 345 350 Ser Leu Pro Val Ser Arg Pro Ile Ser Pro Ser Pro Ser Ala IleLeu 355 360 365 Glu Arg Arg Asp Val Lys Pro Asp Glu Asp Met Ser Gly LysAsn Ile 370 375 380 Ala Met Tyr Arg Asn Glu Gly Phe Tyr Ala Asp Pro TyrLeu Tyr His 385 390 395 400 Glu Gly Arg Met Ser Ile Ala Ser Ser His GlyGly His Pro Leu Asp 405 410 415 Val Pro Asp His Ile Ile Ala Tyr His ArgThr Ala Ile Arg Ser Ala 420 425 430 Ser Ala Tyr Cys Asn Pro Ser Met GlnAla Glu Met His Met Glu Gln 435 440 445 Ser Leu Tyr Arg Gln Lys Ser ArgLys Tyr Pro Asp Ser His Leu Pro 450 455 460 Thr Leu Gly Ser Lys Thr ProPro Ala Ser Pro His Arg Val Ser Asp 465 470 475 480 Leu Arg Met Ile AspMet His Ala His Tyr Asn Ala His Gly Pro Pro 485 490 495 His Thr Met GlnPro Asp Arg Ala Ser Pro Ser Arg Gln Ala Phe Lys 500 505 510 Lys Glu ProGly Thr Leu Val Tyr Ile Glu Lys Pro Arg Ser Ala Ala 515 520 525 Gly LeuSer Ser Leu Val Asp Leu Gly Pro Pro Leu Met Glu Lys Gln 530 535 540 ValPhe Ala Tyr Ser Thr Ala Thr Ile Pro Lys Asp Arg Glu Thr Ser 545 550 555560 Glu Lys Met Met Lys Thr Thr Ala Asn Arg Asn His Thr Asp Ser Ala 565570 575 Gly Thr Pro His Val Ser Gly Gly Lys Met Leu Ser Ala Leu Glu Ser580 585 590 Thr Val Pro Pro Ser Gln Pro Pro Pro Val Gly Thr Ser Ala IleHis 595 600 605 Met Ser Leu Leu Glu Met Arg Arg Ser Val Ala Glu Leu ArgLeu Gln 610 615 620 Leu Gln Gln Met Arg Gln Leu Gln Leu Gln Asn Gln GluLeu Leu Arg 625 630 635 640 Ala Met Met Lys Lys Ala Glu Leu Glu Ile SerGly Lys Val Met Glu 645 650 655 Thr Met Lys Arg Leu Glu Asp Pro Val GlnArg Gln Arg Val Leu Val 660 665 670 Glu Gln Glu Arg Gln Lys Tyr Leu HisGlu Glu Glu Lys Ile Val Lys 675 680 685 Lys Leu Cys Glu Leu Glu Asp PheVal Glu Asp Leu Lys Lys Asp Ser 690 695 700 Thr Ala Ala Ser Arg Leu ValThr Leu Lys Asp Val Glu Asp Gly Ala 705 710 715 720 Phe Leu Leu Arg GlnVal Gly Glu Ala Val Ala Thr Leu Lys Gly Glu 725 730 735 Phe Pro Thr LeuGln Asn Lys Met Arg Ala Ile Leu Arg Ile Glu Val 740 745 750 Glu Ala ValArg Phe Leu Lys Glu Glu Pro His Lys Leu Asp Ser Leu 755 760 765 Leu LysArg Val Arg Ser Met Thr Asp Val Leu Thr Met Leu Arg Arg 770 775 780 HisVal Thr Asp Gly Leu Leu Lys Gly Thr Asp Ala Ala Gln Ala Ala 785 790 795800 Gln Tyr Met Ala Met Glu Lys Ala Thr Ala Ala Glu Val Leu Lys Ser 805810 815 Gln Glu Glu Ala Ala His Thr Ser Gly Gln Pro Phe His Ser Thr Gly820 825 830 Ala Pro Gly Asp Ala Lys Ser Glu Val Val Pro Leu Ser Gly MetMet 835 840 845 Val Arg His Ala Gln Ser Ser Pro Val Val Ile Gln Pro SerGln His 850 855 860 Ser Val Ala Leu Leu Asn Pro Ala Gln Asn Leu Pro HisVal Ala Ser 865 870 875 880 Ser Pro Ala Val Pro Gln Glu Ala Thr Ser ThrLeu Gln Met Ser Gln 885 890 895 Ala Pro Gln Ser Pro Gln Ile Pro Met AsnGly Ser Ala Met Gln Ser 900 905 910 Leu Phe Ile Glu Glu Ile His Ser ValSer Ala Lys Asn Arg Ala Val 915 920 925 Ser Ile Glu Lys Ala Glu Lys LysTrp Glu Glu Lys Arg Gln Asn Leu 930 935 940 Asp His Tyr Asn Gly Lys GluPhe Glu Lys Leu Leu Glu Glu Ala Gln 945 950 955 960 Ala Asn Ile Met LysSer Ile Pro Asn Leu Glu Met Pro Pro Ala Thr 965 970 975 Gly Pro Leu ProArg Gly Asp Ala Pro Val Asp Lys Val Glu Leu Ser 980 985 990 Glu Asp SerPro Asn Ser Glu Gln Asp Leu Glu Lys Leu Gly Gly Lys 995 1000 1005 SerPro Pro Pro Pro Pro Pro Pro Pro Arg Arg Ser Tyr Leu Pro 1010 1015 1020Gly Ser Gly Leu Thr Thr Thr Arg Ser Gly Asp Val Val Tyr Thr 1025 10301035 Gly Arg Lys Glu Asn Ile Thr Ala Lys Ala Ser Ser Glu Asp Ala 10401045 1050 Gly Pro Ser Pro Gln Thr Arg Ala Thr Lys Tyr Pro Ala Glu Glu1055 1060 1065 Pro Ala Ser Ala Trp Thr Pro Ser Pro Pro Pro Val Thr ThrSer 1070 1075 1080 Ser Ser Lys Asp Glu Glu Glu Glu Glu Glu Glu Gly AspLys Ile 1085 1090 1095 Met Ala Glu Leu Gln Ala Phe Gln Lys Cys Ser PheMet Asp Val 1100 1105 1110 Asn Ser Asn Ser His Ala Glu Pro Ser Arg AlaAsp Ser His Val 1115 1120 1125 Lys Asp Thr Arg Ser Gly Ala Thr Val ProPro Lys Glu Lys Lys 1130 1135 1140 Asn Leu Glu Phe Phe His Glu Asp ValArg Lys Ser Asp Val Glu 1145 1150 1155 Tyr Glu Asn Gly Pro Gln Met GluPhe Gln Lys Val Thr Thr Gly 1160 1165 1170 Ala Val Arg Pro Ser Asp ProPro Lys Trp Glu Arg Gly Met Glu 1175 1180 1185 Asn Ser Ile Ser Asp AlaSer Arg Thr Ser Glu Tyr Lys Thr Glu 1190 1195 1200 Ile Ile Met Lys GluAsn Ser Ile Ser Asn Met Ser Leu Leu Arg 1205 1210 1215 Asp Ser Arg AsnTyr Ser Gln Glu Thr Val Pro Lys Ala Ser Phe 1220 1225 1230 Gly Phe SerGly Ile Ser Pro Leu Glu Asp Glu Ile Asn Lys Gly 1235 1240 1245 Ser LysIle Ser Gly Leu Gln Tyr Ser Ile Pro Asp Thr Glu Asn 1250 1255 1260 GlnThr Leu Asn Tyr Gly Lys Thr Lys Glu Met Glu Lys Gln Asn 1265 1270 1275Thr Asp Lys Cys His Val Ser Ser His Thr Arg Leu Thr Glu Ser 1280 12851290 Ser Val His Asp Phe Lys Thr Glu Asp Gln Glu Val Ile Thr Thr 12951300 1305 Asp Phe Gly Gln Val Val Leu Arg Pro Lys Glu Ala Arg His Ala1310 1315 1320 Asn Val Asn Pro Asn Glu Asp Gly Glu Ser Ser Ser Ser SerPro 1325 1330 1335 Thr Glu Glu Asn Ala Ala Thr Asp Asn Ile Ala Phe MetIle Thr 1340 1345 1350 Glu Thr Thr Val Gln Val Leu Ser Ser Gly Glu ValHis Asp Ile 1355 1360 1365 Val Ser Gln Lys Gly Glu Asp Ile Gln Thr ValAsn Ile Asp Ala 1370 1375 1380 Arg Lys Glu Met Thr Pro Arg Gln Glu GlyThr Asp Asn Glu Asp 1385 1390 1395 Pro Val Val Cys Leu Asp Lys Lys ProVal Ile Ile Ile Phe Asp 1400 1405 1410 Glu Pro Met Asp Ile Arg Ser AlaTyr Lys Arg Leu Ser Thr Ile 1415 1420 1425 Phe Glu Glu Cys Asp Glu GluLeu Glu Arg Met Met Met Glu Glu 1430 1435 1440 Lys Ile Glu Glu Glu GluGlu Glu Glu Asn Gly Asp Ser Val Val 1445 1450 1455 Gln Asn Asn Asn ThrSer Gln Met Ser His Lys Lys Val Ala Pro 1460 1465 1470 Gly Asn Leu ArgThr Gly Gln Gln Val Glu Thr Lys Ser Gln Pro 1475 1480 1485 His Ser LeuAla Thr Glu Thr Arg Asn Pro Gly Gly Gln Glu Met 1490 1495 1500 Asn ArgThr Glu Leu Asn Lys Phe Ser His Val Asp Ser Pro Asn 1505 1510 1515 SerGlu Cys Lys Gly Glu Asp Ala Thr Asp Asp Gln Phe Glu Ser 1520 1525 1530Pro Lys Lys Lys Phe Lys Phe Lys Phe Pro Lys Lys Gln Leu Ala 1535 15401545 Ala Leu Thr Gln Ala Ile Arg Thr Gly Thr Lys Thr Gly Lys Lys 15501555 1560 Thr Leu Gln Val Val Val Tyr Glu Glu Glu Glu Glu Asp Gly Thr1565 1570 1575 Leu Lys Gln His Lys Glu Ala Lys Arg Phe Glu Ile Ala ArgSer 1580 1585 1590 Gln Pro Glu Asp Thr Pro Glu Asn Thr Val Arg Arg GlnGlu Gln 1595 1600 1605 Pro Ser Ile Glu Ser Thr Ser Pro Ile Ser Arg ThrAsp Glu Ile 1610 1615 1620 Arg Lys Asn Thr Tyr Arg Thr Leu Asp Ser LeuGlu Gln Thr Ile 1625 1630 1635 Lys Gln Leu Glu Asn Thr Ile Ser Glu MetSer Pro Lys Ala Leu 1640 1645 1650 Val Asp Thr Ser Cys Ser Ser Asn ArgAsp Ser Val Ala Ser Ser 1655 1660 1665 Ser His Ile Ala Gln Glu Ala SerPro Arg Pro Leu Leu Val Pro 1670 1675 1680 Asp Glu Gly Pro Thr Ala LeuGlu Pro Pro Thr Ser Ile Pro Ser 1685 1690 1695 Ala Ser Arg Lys Val SerTrp Ser Ala Gly Lys 1700 1705 14 7140 DNA Homo sapiens CDS (1)..(5724)14 atg gaa gaa aat gaa agc cag aaa tgt gag ccg tgc ctt cct tac tca 48Met Glu Glu Asn Glu Ser Gln Lys Cys Glu Pro Cys Leu Pro Tyr Ser 1 5 1015 gca gac aga aga cag atg cag gaa caa ggc aaa ggc aat ctg cat gta 96Ala Asp Arg Arg Gln Met Gln Glu Gln Gly Lys Gly Asn Leu His Val 20 25 30aca tca cca gaa gat gca gaa tgc cgc aga acc aag gaa cgc ctt tct 144 ThrSer Pro Glu Asp Ala Glu Cys Arg Arg Thr Lys Glu Arg Leu Ser 35 40 45 aatgga aac agt cgt ggt tca gtt tcc aag tct tcc cgc aat atc cca 192 Asn GlyAsn Ser Arg Gly Ser Val Ser Lys Ser Ser Arg Asn Ile Pro 50 55 60 agg agacac acc cta ggg ggg ccc cga agt tcc aag gaa ata ctg gga 240 Arg Arg HisThr Leu Gly Gly Pro Arg Ser Ser Lys Glu Ile Leu Gly 65 70 75 80 atg caaaca tct gag atg gat cgg aag aga gaa gcg ttc cta gaa cat 288 Met Gln ThrSer Glu Met Asp Arg Lys Arg Glu Ala Phe Leu Glu His 85 90 95 ctg aag cagaag tac ccc cac cac gcc tct gca atc atg ggt cac caa 336 Leu Lys Gln LysTyr Pro His His Ala Ser Ala Ile Met Gly His Gln 100 105 110 gag agg ctgaga gac cag aca agg agc ccc aaa ctg tct cac agt cct 384 Glu Arg Leu ArgAsp Gln Thr Arg Ser Pro Lys Leu Ser His Ser Pro 115 120 125 caa cca cccagt ctg ggt gac ccg gtc gag cat tta tca gag acg tcc 432 Gln Pro Pro SerLeu Gly Asp Pro Val Glu His Leu Ser Glu Thr Ser 130 135 140 gct gat tctttg gaa gcc atg tct gag ggg gat gct cca acc cct ttt 480 Ala Asp Ser LeuGlu Ala Met Ser Glu Gly Asp Ala Pro Thr Pro Phe 145 150 155 160 tcc agaggc agc cgg act cgt gcg agc ctt cct gtg gtg agg tca acc 528 Ser Arg GlySer Arg Thr Arg Ala Ser Leu Pro Val Val Arg Ser Thr 165 170 175 aac cagacg aaa gaa aga tct ctg ggg gtt ctc tat ctc cag tat gga 576 Asn Gln ThrLys Glu Arg Ser Leu Gly Val Leu Tyr Leu Gln Tyr Gly 180 185 190 gat gaaacc aag cag ctc agg atg ccg aat gaa atc aca agt gca gac 624 Asp Glu ThrLys Gln Leu Arg Met Pro Asn Glu Ile Thr Ser Ala Asp 195 200 205 aca atccgt gct ctc ttc gta agt gcc ttt cca cag cag ctc acc atg 672 Thr Ile ArgAla Leu Phe Val Ser Ala Phe Pro Gln Gln Leu Thr Met 210 215 220 aaa atgctg gaa tcg ccc agt gtc gcc att tac atc aaa gat gaa agc 720 Lys Met LeuGlu Ser Pro Ser Val Ala Ile Tyr Ile Lys Asp Glu Ser 225 230 235 240 agaaat gtc tat tat gaa tta aat gat gta agg aac att caa gac aga 768 Arg AsnVal Tyr Tyr Glu Leu Asn Asp Val Arg Asn Ile Gln Asp Arg 245 250 255 tcactc ctc aaa gtg tac aac aag gat cct gca cat gcg ttt aat cac 816 Ser LeuLeu Lys Val Tyr Asn Lys Asp Pro Ala His Ala Phe Asn His 260 265 270 acacca aaa act atg aat gga gac atg agg atg cag aga gaa ctt gtt 864 Thr ProLys Thr Met Asn Gly Asp Met Arg Met Gln Arg Glu Leu Val 275 280 285 tatgca aga gga gat ggc cct ggg gcc cct cgc ccc gga tct act gct 912 Tyr AlaArg Gly Asp Gly Pro Gly Ala Pro Arg Pro Gly Ser Thr Ala 290 295 300 catcca ccc cat gcg att cca aat tcc cca ccg tct act cca gtg ccc 960 His ProPro His Ala Ile Pro Asn Ser Pro Pro Ser Thr Pro Val Pro 305 310 315 320cat tcc atg ccc ccc tcc ccg tcc aga att cct tat ggg ggc acc cgc 1008 HisSer Met Pro Pro Ser Pro Ser Arg Ile Pro Tyr Gly Gly Thr Arg 325 330 335tcc atg gtt gtt cct ggc aat gcc acc atc ccc agg gac aga atc tcc 1056 SerMet Val Val Pro Gly Asn Ala Thr Ile Pro Arg Asp Arg Ile Ser 340 345 350agc ctg cca gtc tcc aga ccc atc tct cca agc cca agc gcc att tta 1104 SerLeu Pro Val Ser Arg Pro Ile Ser Pro Ser Pro Ser Ala Ile Leu 355 360 365gaa aga aga gat gtc aag cct gat gaa gac atg agt ggc aaa aac att 1152 GluArg Arg Asp Val Lys Pro Asp Glu Asp Met Ser Gly Lys Asn Ile 370 375 380gca atg tac aga aat gag ggt ttc tat gct gat cct tac ctt tat cac 1200 AlaMet Tyr Arg Asn Glu Gly Phe Tyr Ala Asp Pro Tyr Leu Tyr His 385 390 395400 gag gga cgg atg agc ata gcc tca tcc cat ggt gga cac cca ctg gat 1248Glu Gly Arg Met Ser Ile Ala Ser Ser His Gly Gly His Pro Leu Asp 405 410415 gtc ccc gac cac atc att gca tat cac cgc acc gcc atc cgg tca gcg 1296Val Pro Asp His Ile Ile Ala Tyr His Arg Thr Ala Ile Arg Ser Ala 420 425430 agt gct tat tgt aac ccc tca atg caa gcg gaa atg cat atg gaa caa 1344Ser Ala Tyr Cys Asn Pro Ser Met Gln Ala Glu Met His Met Glu Gln 435 440445 tca ctg tac aga cag aaa tca agg aaa tat ccg gat agc cat ttg cct 1392Ser Leu Tyr Arg Gln Lys Ser Arg Lys Tyr Pro Asp Ser His Leu Pro 450 455460 aca ctg ggc tcc aaa aca ccc cct gcc tct cct cac aga gtc agt gac 1440Thr Leu Gly Ser Lys Thr Pro Pro Ala Ser Pro His Arg Val Ser Asp 465 470475 480 ctg agg atg ata gac atg cac gct cac tat aat gcc cac ggc ccc cct1488 Leu Arg Met Ile Asp Met His Ala His Tyr Asn Ala His Gly Pro Pro 485490 495 cac acc atg cag cca gac cgg gcc tct ccg agc cgc cag gcc ttt aaa1536 His Thr Met Gln Pro Asp Arg Ala Ser Pro Ser Arg Gln Ala Phe Lys 500505 510 aag gag cca ggc acc ttg gtg tat ata gaa aag cca cgg agc gct gca1584 Lys Glu Pro Gly Thr Leu Val Tyr Ile Glu Lys Pro Arg Ser Ala Ala 515520 525 gga tta tcc agc ctt gta gac ctc ggc cct cct cta atg gag aag caa1632 Gly Leu Ser Ser Leu Val Asp Leu Gly Pro Pro Leu Met Glu Lys Gln 530535 540 gtt ttt gcc tac agc acg gcg aca ata ccc aaa gac aga gag acc agc1680 Val Phe Ala Tyr Ser Thr Ala Thr Ile Pro Lys Asp Arg Glu Thr Ser 545550 555 560 gag aaa atg atg aaa acc aca gcc aac agg aac cac aca gat agtgca 1728 Glu Lys Met Met Lys Thr Thr Ala Asn Arg Asn His Thr Asp Ser Ala565 570 575 gga acg ccc cat gtg tct ggt ggg aag atg ctc agt gct ctg gagtcc 1776 Gly Thr Pro His Val Ser Gly Gly Lys Met Leu Ser Ala Leu Glu Ser580 585 590 acg gtg cct ccc agc cag cct cca cct gtg ggc acc tca gcc atccac 1824 Thr Val Pro Pro Ser Gln Pro Pro Pro Val Gly Thr Ser Ala Ile His595 600 605 atg agc ctg ctt gag atg agg cgg agc gtg gcg gaa ctc agg ctccag 1872 Met Ser Leu Leu Glu Met Arg Arg Ser Val Ala Glu Leu Arg Leu Gln610 615 620 ctc cag cag atg cgg cag ctc cag ctg cag aac cag gag ttg ctgagg 1920 Leu Gln Gln Met Arg Gln Leu Gln Leu Gln Asn Gln Glu Leu Leu Arg625 630 635 640 gca atg atg aag aag gcc gag ctg gaa atc agt ggc aaa gtgatg gaa 1968 Ala Met Met Lys Lys Ala Glu Leu Glu Ile Ser Gly Lys Val MetGlu 645 650 655 aca atg aag aga ctg gag gat ccc gtg cag cga cag cgc gtccta gtg 2016 Thr Met Lys Arg Leu Glu Asp Pro Val Gln Arg Gln Arg Val LeuVal 660 665 670 gag caa gag aga caa aaa tat ctt cat gag gaa gag aag atcgtc aag 2064 Glu Gln Glu Arg Gln Lys Tyr Leu His Glu Glu Glu Lys Ile ValLys 675 680 685 aag ttg tgc gag ttg gaa gac ttt gtt gaa gac ttg aag aaggac tcc 2112 Lys Leu Cys Glu Leu Glu Asp Phe Val Glu Asp Leu Lys Lys AspSer 690 695 700 acg gca gcc agc cga ttg gtt act ctg aaa gac gtg gaa gacggg gct 2160 Thr Ala Ala Ser Arg Leu Val Thr Leu Lys Asp Val Glu Asp GlyAla 705 710 715 720 ttc ctc ctg cgt caa gtg gga gag gct gta gct acc ctgaaa gga gaa 2208 Phe Leu Leu Arg Gln Val Gly Glu Ala Val Ala Thr Leu LysGly Glu 725 730 735 ttt cca acc tta caa aac aag atg cga gcc atc ctg cgcata gaa gtg 2256 Phe Pro Thr Leu Gln Asn Lys Met Arg Ala Ile Leu Arg IleGlu Val 740 745 750 gag gcc gtg cgg ttt ctg aag gag gag cca cac aag ctggac agt ctc 2304 Glu Ala Val Arg Phe Leu Lys Glu Glu Pro His Lys Leu AspSer Leu 755 760 765 ctg aag cgt gtg cgc agc atg aca gac gtc ctg acc atgctg cgg aga 2352 Leu Lys Arg Val Arg Ser Met Thr Asp Val Leu Thr Met LeuArg Arg 770 775 780 cat gtc act gat ggg ctc ctg aaa ggc acg gac gca gcccaa gcc gca 2400 His Val Thr Asp Gly Leu Leu Lys Gly Thr Asp Ala Ala GlnAla Ala 785 790 795 800 cag tac atg gct atg gaa aag gcc aca gcc gca gaagtc ctg aag agt 2448 Gln Tyr Met Ala Met Glu Lys Ala Thr Ala Ala Glu ValLeu Lys Ser 805 810 815 cag gag gag gca gcc cac acc tcc ggc cag ccc ttccac agc aca ggt 2496 Gln Glu Glu Ala Ala His Thr Ser Gly Gln Pro Phe HisSer Thr Gly 820 825 830 gcc cct ggc gat gcg aag tcg gaa gtg gtg cct ttgtcc ggc atg atg 2544 Ala Pro Gly Asp Ala Lys Ser Glu Val Val Pro Leu SerGly Met Met 835 840 845 gtt cgc cac gcg cag agc tcc cct gtg gtc atc cagccc tcc cag cac 2592 Val Arg His Ala Gln Ser Ser Pro Val Val Ile Gln ProSer Gln His 850 855 860 tcc gtg gcc ctg ctg aac cct gct cag aac ttg cctcac gtg gcc agc 2640 Ser Val Ala Leu Leu Asn Pro Ala Gln Asn Leu Pro HisVal Ala Ser 865 870 875 880 tcc cca gcc gtc ccc cag gaa gca acc tcc actctg cag atg tcg cag 2688 Ser Pro Ala Val Pro Gln Glu Ala Thr Ser Thr LeuGln Met Ser Gln 885 890 895 gct ccg cag tcc cca cag ata ccc atg aat gggtct gcc atg cag agc 2736 Ala Pro Gln Ser Pro Gln Ile Pro Met Asn Gly SerAla Met Gln Ser 900 905 910 ttg ttc att gaa gaa atc cac agt gtg agt gccaag aac agg gca gtg 2784 Leu Phe Ile Glu Glu Ile His Ser Val Ser Ala LysAsn Arg Ala Val 915 920 925 tct atc gag aaa gca gaa aag aaa tgg gag gaaaaa agg caa aat ctg 2832 Ser Ile Glu Lys Ala Glu Lys Lys Trp Glu Glu LysArg Gln Asn Leu 930 935 940 gat cac tat aat ggg aaa gag ttt gag aag ctccta gaa gaa gct cag 2880 Asp His Tyr Asn Gly Lys Glu Phe Glu Lys Leu LeuGlu Glu Ala Gln 945 950 955 960 gcc aat atc atg aag tca ata cca aat ctggag atg ccg cca gcc aca 2928 Ala Asn Ile Met Lys Ser Ile Pro Asn Leu GluMet Pro Pro Ala Thr 965 970 975 ggc cca ctg cca agg gga gat gcc cca gtggac aag gtg gaa ctt tca 2976 Gly Pro Leu Pro Arg Gly Asp Ala Pro Val AspLys Val Glu Leu Ser 980 985 990 gaa gat tct cca aat tcg gaa cag gac ttggaa aag ctg ggg gga aag 3024 Glu Asp Ser Pro Asn Ser Glu Gln Asp Leu GluLys Leu Gly Gly Lys 995 1000 1005 tcg ccc cct cct cct ccg cca cct cctcgt cga agc tac ctg cca 3069 Ser Pro Pro Pro Pro Pro Pro Pro Pro Arg ArgSer Tyr Leu Pro 1010 1015 1020 gga tcg gga ctc acc acc acg agg tca ggcgat gtg gtc tac acc 3114 Gly Ser Gly Leu Thr Thr Thr Arg Ser Gly Asp ValVal Tyr Thr 1025 1030 1035 ggc aga aag gag aac atc acc gct aag gca agcagt gaa gat gct 3159 Gly Arg Lys Glu Asn Ile Thr Ala Lys Ala Ser Ser GluAsp Ala 1040 1045 1050 gga cca agc cca cag acc aga gct aca aaa tat ccagca gag gag 3204 Gly Pro Ser Pro Gln Thr Arg Ala Thr Lys Tyr Pro Ala GluGlu 1055 1060 1065 cct gct tca gcc tgg acc cca tcc cca ccg cct gtc accacc tcc 3249 Pro Ala Ser Ala Trp Thr Pro Ser Pro Pro Pro Val Thr Thr Ser1070 1075 1080 tcc tca aag gat gag gag gaa gaa gaa gaa gaa gga gac aaaata 3294 Ser Ser Lys Asp Glu Glu Glu Glu Glu Glu Glu Gly Asp Lys Ile1085 1090 1095 atg gca gaa ctc cag gca ttc cag aag tgt tcc ttt atg gatgta 3339 Met Ala Glu Leu Gln Ala Phe Gln Lys Cys Ser Phe Met Asp Val1100 1105 1110 aat tca aac agt cat gct gag cca tcc cgg gct gac agt cacgtt 3384 Asn Ser Asn Ser His Ala Glu Pro Ser Arg Ala Asp Ser His Val1115 1120 1125 aaa gac act agg tcg ggc gcc aca gtg cca ccc aag gag aagaag 3429 Lys Asp Thr Arg Ser Gly Ala Thr Val Pro Pro Lys Glu Lys Lys1130 1135 1140 aat ttg gaa ttt ttc cat gaa gat gta cgg aaa tct gat gttgaa 3474 Asn Leu Glu Phe Phe His Glu Asp Val Arg Lys Ser Asp Val Glu1145 1150 1155 tat gaa aat ggc ccc caa atg gaa ttc caa aag gtt acc acaggg 3519 Tyr Glu Asn Gly Pro Gln Met Glu Phe Gln Lys Val Thr Thr Gly1160 1165 1170 gct gta aga cct agt gac cct cct aag tgg gaa aga gga atggag 3564 Ala Val Arg Pro Ser Asp Pro Pro Lys Trp Glu Arg Gly Met Glu1175 1180 1185 aat agt att tct gat gca tca aga aca tca gaa tat aaa actgag 3609 Asn Ser Ile Ser Asp Ala Ser Arg Thr Ser Glu Tyr Lys Thr Glu1190 1195 1200 atc ata atg aag gaa aat tcc ata tcc aat atg agt tta ctcaga 3654 Ile Ile Met Lys Glu Asn Ser Ile Ser Asn Met Ser Leu Leu Arg1205 1210 1215 gac agt aga aac tat tcc cag gaa act gtg cct aag gcc agtttc 3699 Asp Ser Arg Asn Tyr Ser Gln Glu Thr Val Pro Lys Ala Ser Phe1220 1225 1230 ggt ttc tct ggc att agt cca tta gaa gat gaa ata aac aaaggg 3744 Gly Phe Ser Gly Ile Ser Pro Leu Glu Asp Glu Ile Asn Lys Gly1235 1240 1245 tct aaa atc tca ggc ctg caa tac tct ata cct gac acc gagaac 3789 Ser Lys Ile Ser Gly Leu Gln Tyr Ser Ile Pro Asp Thr Glu Asn1250 1255 1260 cag acg ctg aat tac gga aag aca aag gag atg gaa aag caaaat 3834 Gln Thr Leu Asn Tyr Gly Lys Thr Lys Glu Met Glu Lys Gln Asn1265 1270 1275 acg gat aag tgt cac gtt tcc tct cac act aga cta aca gaatca 3879 Thr Asp Lys Cys His Val Ser Ser His Thr Arg Leu Thr Glu Ser1280 1285 1290 agc gtg cat gat ttt aaa aca gaa gat caa gag gtt atc acgaca 3924 Ser Val His Asp Phe Lys Thr Glu Asp Gln Glu Val Ile Thr Thr1295 1300 1305 gat ttt ggc caa gtt gtt cta aga ccc aag gag gca agg catgct 3969 Asp Phe Gly Gln Val Val Leu Arg Pro Lys Glu Ala Arg His Ala1310 1315 1320 aac gtg aac cct aat gag gat gga gaa tca agt tca agt tctccc 4014 Asn Val Asn Pro Asn Glu Asp Gly Glu Ser Ser Ser Ser Ser Pro1325 1330 1335 act gaa gaa aat gca gcc act gac aat att gcc ttc atg attacc 4059 Thr Glu Glu Asn Ala Ala Thr Asp Asn Ile Ala Phe Met Ile Thr1340 1345 1350 gaa acc act gtc cag gtt ctt tcc agt ggg gag gtg cat gatatt 4104 Glu Thr Thr Val Gln Val Leu Ser Ser Gly Glu Val His Asp Ile1355 1360 1365 gtt agc caa aag gga gaa gac ata cag acg gtt aat atc gatgcc 4149 Val Ser Gln Lys Gly Glu Asp Ile Gln Thr Val Asn Ile Asp Ala1370 1375 1380 aga aaa gag atg acc ccc cga caa gaa ggg act gac aat gaggat 4194 Arg Lys Glu Met Thr Pro Arg Gln Glu Gly Thr Asp Asn Glu Asp1385 1390 1395 cca gtc gtg tgc ctg gac aag aaa cca gtg atc atc att ttcgat 4239 Pro Val Val Cys Leu Asp Lys Lys Pro Val Ile Ile Ile Phe Asp1400 1405 1410 gag ccc atg gac atc cgg tct gcc tat aag aga ctt tca actatc 4284 Glu Pro Met Asp Ile Arg Ser Ala Tyr Lys Arg Leu Ser Thr Ile1415 1420 1425 ttt gag gaa tgt gat gag gaa tta gag aga atg atg atg gaggaa 4329 Phe Glu Glu Cys Asp Glu Glu Leu Glu Arg Met Met Met Glu Glu1430 1435 1440 aag ata gag gag gag gaa gag gag gaa aat ggg gat tct gtagtc 4374 Lys Ile Glu Glu Glu Glu Glu Glu Glu Asn Gly Asp Ser Val Val1445 1450 1455 cag aat aat aac act tcc cag atg tct cat aag aag gtg gcccca 4419 Gln Asn Asn Asn Thr Ser Gln Met Ser His Lys Lys Val Ala Pro1460 1465 1470 ggc aat ctt aga acc gga caa cag gtg gaa aca aag tca cagcca 4464 Gly Asn Leu Arg Thr Gly Gln Gln Val Glu Thr Lys Ser Gln Pro1475 1480 1485 cac tcc ctg gcc aca gag acc aga aac cca gga gga cag gaaatg 4509 His Ser Leu Ala Thr Glu Thr Arg Asn Pro Gly Gly Gln Glu Met1490 1495 1500 aac aga acg gag ctg aac aag ttc agc cac gtg gat tct ccaaat 4554 Asn Arg Thr Glu Leu Asn Lys Phe Ser His Val Asp Ser Pro Asn1505 1510 1515 tcg gaa tgc aag ggt gag gac gcg acc gat gac cag ttt gaaagc 4599 Ser Glu Cys Lys Gly Glu Asp Ala Thr Asp Asp Gln Phe Glu Ser1520 1525 1530 ccc aag aaa aag ttt aaa ttc aaa ttc cct aag aag caa ctcgcc 4644 Pro Lys Lys Lys Phe Lys Phe Lys Phe Pro Lys Lys Gln Leu Ala1535 1540 1545 gct ctc act caa gcc att cgc acc gga act aaa aca ggg aagaag 4689 Ala Leu Thr Gln Ala Ile Arg Thr Gly Thr Lys Thr Gly Lys Lys1550 1555 1560 act ttg caa gtg gta gtc tat gaa gaa gag gaa gag gat ggcacc 4734 Thr Leu Gln Val Val Val Tyr Glu Glu Glu Glu Glu Asp Gly Thr1565 1570 1575 ctg aaa cag cac aaa gaa gcc aag cgc ttc gaa atc gct aggtct 4779 Leu Lys Gln His Lys Glu Ala Lys Arg Phe Glu Ile Ala Arg Ser1580 1585 1590 caa cct gaa gac acc cct gaa aac aca gtg agg agg caa gagcag 4824 Gln Pro Glu Asp Thr Pro Glu Asn Thr Val Arg Arg Gln Glu Gln1595 1600 1605 ccc agc atc gag agt aca tct ccg att tca aga act gat gaaatt 4869 Pro Ser Ile Glu Ser Thr Ser Pro Ile Ser Arg Thr Asp Glu Ile1610 1615 1620 aga aaa aac acc tac aga aca ttg gat agc ctg gag cag accatt 4914 Arg Lys Asn Thr Tyr Arg Thr Leu Asp Ser Leu Glu Gln Thr Ile1625 1630 1635 aaa cag ctc gaa aat aca atc agt gaa atg agt ccc aaa gcccta 4959 Lys Gln Leu Glu Asn Thr Ile Ser Glu Met Ser Pro Lys Ala Leu1640 1645 1650 gtt gat acc tca tgt tct tcc aac aga gat tct gtt gca agttca 5004 Val Asp Thr Ser Cys Ser Ser Asn Arg Asp Ser Val Ala Ser Ser1655 1660 1665 tcc cac ata gcc caa gag gcc tct ccc cga ccc ttg cta gttccg 5049 Ser His Ile Ala Gln Glu Ala Ser Pro Arg Pro Leu Leu Val Pro1670 1675 1680 gat gaa ggt ccc act gcc cta gag ccc cct acg tcg ata ccttca 5094 Asp Glu Gly Pro Thr Ala Leu Glu Pro Pro Thr Ser Ile Pro Ser1685 1690 1695 gct tca cgt aag ggc tcc agc ggg gcc cca cag acg agc aggatg 5139 Ala Ser Arg Lys Gly Ser Ser Gly Ala Pro Gln Thr Ser Arg Met1700 1705 1710 cct gtc ccc atg agt gcc aag aac aga ccc gga acc ctg gacaaa 5184 Pro Val Pro Met Ser Ala Lys Asn Arg Pro Gly Thr Leu Asp Lys1715 1720 1725 ccc ggc aag cag tcc aaa ctg cag gat ccc cgc caa tat cgtcag 5229 Pro Gly Lys Gln Ser Lys Leu Gln Asp Pro Arg Gln Tyr Arg Gln1730 1735 1740 gct aat gga agt gct aag aaa tct ggt ggg gac ttt aag cctact 5274 Ala Asn Gly Ser Ala Lys Lys Ser Gly Gly Asp Phe Lys Pro Thr1745 1750 1755 tcc ccc tcc tta cct gct tct aag att cca gcc ctt tct cccagc 5319 Ser Pro Ser Leu Pro Ala Ser Lys Ile Pro Ala Leu Ser Pro Ser1760 1765 1770 tct ggg aaa agc agt tct ctg ccc tct tct agt ggt gac agctct 5364 Ser Gly Lys Ser Ser Ser Leu Pro Ser Ser Ser Gly Asp Ser Ser1775 1780 1785 aac ctc cct aat cca cct gct act aaa cca tcg att gct tctaac 5409 Asn Leu Pro Asn Pro Pro Ala Thr Lys Pro Ser Ile Ala Ser Asn1790 1795 1800 cct ctc agc ccc caa aca gga cca cct gct cac tct gcc tccctc 5454 Pro Leu Ser Pro Gln Thr Gly Pro Pro Ala His Ser Ala Ser Leu1805 1810 1815 atc cct tct gtc tct aat ggc tct ttg aag ttt cag agc ctcact 5499 Ile Pro Ser Val Ser Asn Gly Ser Leu Lys Phe Gln Ser Leu Thr1820 1825 1830 cat aca ggt aaa ggt cac cat ctt tca ttc tca ccg cag agtcaa 5544 His Thr Gly Lys Gly His His Leu Ser Phe Ser Pro Gln Ser Gln1835 1840 1845 aat ggc cga gca ccc cct cct ttg tca ttt tcc tcc tcc cctcct 5589 Asn Gly Arg Ala Pro Pro Pro Leu Ser Phe Ser Ser Ser Pro Pro1850 1855 1860 tct cct gcc tcc tcc gtc tca ctg aat caa ggt gcc aag ggcacc 5634 Ser Pro Ala Ser Ser Val Ser Leu Asn Gln Gly Ala Lys Gly Thr1865 1870 1875 agg acc atc cat act ccc agc ctc acc agc tac aag gca cagaat 5679 Arg Thr Ile His Thr Pro Ser Leu Thr Ser Tyr Lys Ala Gln Asn1880 1885 1890 gga agt tca agc aaa gcc acc cca tcc aca gca aaa gaa acctct 5724 Gly Ser Ser Ser Lys Ala Thr Pro Ser Thr Ala Lys Glu Thr Ser1895 1900 1905 taaaggtcaa atcctattag gcacaagtcg gagttacatt taaaaaaaattaacagtcta 5784 caacaactgt tttcacaaga gaatgtaaca tattgctgta tcgtttgaggcttaatgcta 5844 aatatgtgct aaatactgga ttaatagatt tcagtaaagc tcgttcgttttgtttggttt 5904 tctttttacc tagttgctat agtgtctaca gtctatactc aatacctataaaatgcagta 5964 agcatgtgtt acagaaagag gttctggtgg gagagaaagg tgcgtgtgagacaggagaat 6024 tgtcttaagc atataaaaca tgtatgattc cagaatttta gtatgttttgtataaaacta 6084 tttttcatta cggagactag aagtgaacag agaattacac aagtgtgactatacaaattg 6144 taaaacagat actataatat ttccttttat tttagtgtta tttagctttattacagattt 6204 ctatttttgt caaaacttca tggttccttt caagatcttt tttgccaaaacattttgata 6264 ctatagcatt gtacatttga aagtagtgtt ctagactata aaaccaatgaacttctacat 6324 gagccctaca gacaggcatg tgtagaaggc aatttatcaa acctattgcactgccatgaa 6384 aagtgtgtat aataatttgc tagcccaagc aagctagttt tctttgcttgcttcttttct 6444 ttcttttttc cttccttttt tttttttttt tcttttttaa catgttgagattctctagtt 6504 gttttctttg gcgtatctaa ccccttcttt tgttttctga gacctggtaacccacgctct 6564 tgcattgtgg attttaaaat gtatactctg tacggttctg taaaccgaaaaacttttgta 6624 aatatataaa tatacataga cataaaaata ctgtatgtga cagcacatagagtagttttc 6684 ccacaccaaa gttaattttt atgcatgctt taaaagtata tatcgggaccggcagaaatg 6744 gaagtatcca tacattttta aaaagcaaca agtttgcaca gctagagtgtttttgtaaat 6804 aaatgtattt gtataacaca gtcatgtaat atacagaact ataagcagagactttgcaaa 6864 actaaataaa gggctgcatg cttattattt tttgtacctt gtcactataactacttccta 6924 gtcaaagaac gaaatgtaac tgttaccgag ttaaatgttt ttccgctttgagggatgtaa 6984 ccacatccac tcagaggaca ctacttttct gaaagctctg gggtgactaatgatgagttc 7044 ctaataaatt aattgcaagt gtggtgcctt ggaaaaaaaa aaaaaaaaaaaaaaaaaaaa 7104 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaa 7140 15 1908 PRTHomo sapiens 15 Met Glu Glu Asn Glu Ser Gln Lys Cys Glu Pro Cys Leu ProTyr Ser 1 5 10 15 Ala Asp Arg Arg Gln Met Gln Glu Gln Gly Lys Gly AsnLeu His Val 20 25 30 Thr Ser Pro Glu Asp Ala Glu Cys Arg Arg Thr Lys GluArg Leu Ser 35 40 45 Asn Gly Asn Ser Arg Gly Ser Val Ser Lys Ser Ser ArgAsn Ile Pro 50 55 60 Arg Arg His Thr Leu Gly Gly Pro Arg Ser Ser Lys GluIle Leu Gly 65 70 75 80 Met Gln Thr Ser Glu Met Asp Arg Lys Arg Glu AlaPhe Leu Glu His 85 90 95 Leu Lys Gln Lys Tyr Pro His His Ala Ser Ala IleMet Gly His Gln 100 105 110 Glu Arg Leu Arg Asp Gln Thr Arg Ser Pro LysLeu Ser His Ser Pro 115 120 125 Gln Pro Pro Ser Leu Gly Asp Pro Val GluHis Leu Ser Glu Thr Ser 130 135 140 Ala Asp Ser Leu Glu Ala Met Ser GluGly Asp Ala Pro Thr Pro Phe 145 150 155 160 Ser Arg Gly Ser Arg Thr ArgAla Ser Leu Pro Val Val Arg Ser Thr 165 170 175 Asn Gln Thr Lys Glu ArgSer Leu Gly Val Leu Tyr Leu Gln Tyr Gly 180 185 190 Asp Glu Thr Lys GlnLeu Arg Met Pro Asn Glu Ile Thr Ser Ala Asp 195 200 205 Thr Ile Arg AlaLeu Phe Val Ser Ala Phe Pro Gln Gln Leu Thr Met 210 215 220 Lys Met LeuGlu Ser Pro Ser Val Ala Ile Tyr Ile Lys Asp Glu Ser 225 230 235 240 ArgAsn Val Tyr Tyr Glu Leu Asn Asp Val Arg Asn Ile Gln Asp Arg 245 250 255Ser Leu Leu Lys Val Tyr Asn Lys Asp Pro Ala His Ala Phe Asn His 260 265270 Thr Pro Lys Thr Met Asn Gly Asp Met Arg Met Gln Arg Glu Leu Val 275280 285 Tyr Ala Arg Gly Asp Gly Pro Gly Ala Pro Arg Pro Gly Ser Thr Ala290 295 300 His Pro Pro His Ala Ile Pro Asn Ser Pro Pro Ser Thr Pro ValPro 305 310 315 320 His Ser Met Pro Pro Ser Pro Ser Arg Ile Pro Tyr GlyGly Thr Arg 325 330 335 Ser Met Val Val Pro Gly Asn Ala Thr Ile Pro ArgAsp Arg Ile Ser 340 345 350 Ser Leu Pro Val Ser Arg Pro Ile Ser Pro SerPro Ser Ala Ile Leu 355 360 365 Glu Arg Arg Asp Val Lys Pro Asp Glu AspMet Ser Gly Lys Asn Ile 370 375 380 Ala Met Tyr Arg Asn Glu Gly Phe TyrAla Asp Pro Tyr Leu Tyr His 385 390 395 400 Glu Gly Arg Met Ser Ile AlaSer Ser His Gly Gly His Pro Leu Asp 405 410 415 Val Pro Asp His Ile IleAla Tyr His Arg Thr Ala Ile Arg Ser Ala 420 425 430 Ser Ala Tyr Cys AsnPro Ser Met Gln Ala Glu Met His Met Glu Gln 435 440 445 Ser Leu Tyr ArgGln Lys Ser Arg Lys Tyr Pro Asp Ser His Leu Pro 450 455 460 Thr Leu GlySer Lys Thr Pro Pro Ala Ser Pro His Arg Val Ser Asp 465 470 475 480 LeuArg Met Ile Asp Met His Ala His Tyr Asn Ala His Gly Pro Pro 485 490 495His Thr Met Gln Pro Asp Arg Ala Ser Pro Ser Arg Gln Ala Phe Lys 500 505510 Lys Glu Pro Gly Thr Leu Val Tyr Ile Glu Lys Pro Arg Ser Ala Ala 515520 525 Gly Leu Ser Ser Leu Val Asp Leu Gly Pro Pro Leu Met Glu Lys Gln530 535 540 Val Phe Ala Tyr Ser Thr Ala Thr Ile Pro Lys Asp Arg Glu ThrSer 545 550 555 560 Glu Lys Met Met Lys Thr Thr Ala Asn Arg Asn His ThrAsp Ser Ala 565 570 575 Gly Thr Pro His Val Ser Gly Gly Lys Met Leu SerAla Leu Glu Ser 580 585 590 Thr Val Pro Pro Ser Gln Pro Pro Pro Val GlyThr Ser Ala Ile His 595 600 605 Met Ser Leu Leu Glu Met Arg Arg Ser ValAla Glu Leu Arg Leu Gln 610 615 620 Leu Gln Gln Met Arg Gln Leu Gln LeuGln Asn Gln Glu Leu Leu Arg 625 630 635 640 Ala Met Met Lys Lys Ala GluLeu Glu Ile Ser Gly Lys Val Met Glu 645 650 655 Thr Met Lys Arg Leu GluAsp Pro Val Gln Arg Gln Arg Val Leu Val 660 665 670 Glu Gln Glu Arg GlnLys Tyr Leu His Glu Glu Glu Lys Ile Val Lys 675 680 685 Lys Leu Cys GluLeu Glu Asp Phe Val Glu Asp Leu Lys Lys Asp Ser 690 695 700 Thr Ala AlaSer Arg Leu Val Thr Leu Lys Asp Val Glu Asp Gly Ala 705 710 715 720 PheLeu Leu Arg Gln Val Gly Glu Ala Val Ala Thr Leu Lys Gly Glu 725 730 735Phe Pro Thr Leu Gln Asn Lys Met Arg Ala Ile Leu Arg Ile Glu Val 740 745750 Glu Ala Val Arg Phe Leu Lys Glu Glu Pro His Lys Leu Asp Ser Leu 755760 765 Leu Lys Arg Val Arg Ser Met Thr Asp Val Leu Thr Met Leu Arg Arg770 775 780 His Val Thr Asp Gly Leu Leu Lys Gly Thr Asp Ala Ala Gln AlaAla 785 790 795 800 Gln Tyr Met Ala Met Glu Lys Ala Thr Ala Ala Glu ValLeu Lys Ser 805 810 815 Gln Glu Glu Ala Ala His Thr Ser Gly Gln Pro PheHis Ser Thr Gly 820 825 830 Ala Pro Gly Asp Ala Lys Ser Glu Val Val ProLeu Ser Gly Met Met 835 840 845 Val Arg His Ala Gln Ser Ser Pro Val ValIle Gln Pro Ser Gln His 850 855 860 Ser Val Ala Leu Leu Asn Pro Ala GlnAsn Leu Pro His Val Ala Ser 865 870 875 880 Ser Pro Ala Val Pro Gln GluAla Thr Ser Thr Leu Gln Met Ser Gln 885 890 895 Ala Pro Gln Ser Pro GlnIle Pro Met Asn Gly Ser Ala Met Gln Ser 900 905 910 Leu Phe Ile Glu GluIle His Ser Val Ser Ala Lys Asn Arg Ala Val 915 920 925 Ser Ile Glu LysAla Glu Lys Lys Trp Glu Glu Lys Arg Gln Asn Leu 930 935 940 Asp His TyrAsn Gly Lys Glu Phe Glu Lys Leu Leu Glu Glu Ala Gln 945 950 955 960 AlaAsn Ile Met Lys Ser Ile Pro Asn Leu Glu Met Pro Pro Ala Thr 965 970 975Gly Pro Leu Pro Arg Gly Asp Ala Pro Val Asp Lys Val Glu Leu Ser 980 985990 Glu Asp Ser Pro Asn Ser Glu Gln Asp Leu Glu Lys Leu Gly Gly Lys 9951000 1005 Ser Pro Pro Pro Pro Pro Pro Pro Pro Arg Arg Ser Tyr Leu Pro1010 1015 1020 Gly Ser Gly Leu Thr Thr Thr Arg Ser Gly Asp Val Val TyrThr 1025 1030 1035 Gly Arg Lys Glu Asn Ile Thr Ala Lys Ala Ser Ser GluAsp Ala 1040 1045 1050 Gly Pro Ser Pro Gln Thr Arg Ala Thr Lys Tyr ProAla Glu Glu 1055 1060 1065 Pro Ala Ser Ala Trp Thr Pro Ser Pro Pro ProVal Thr Thr Ser 1070 1075 1080 Ser Ser Lys Asp Glu Glu Glu Glu Glu GluGlu Gly Asp Lys Ile 1085 1090 1095 Met Ala Glu Leu Gln Ala Phe Gln LysCys Ser Phe Met Asp Val 1100 1105 1110 Asn Ser Asn Ser His Ala Glu ProSer Arg Ala Asp Ser His Val 1115 1120 1125 Lys Asp Thr Arg Ser Gly AlaThr Val Pro Pro Lys Glu Lys Lys 1130 1135 1140 Asn Leu Glu Phe Phe HisGlu Asp Val Arg Lys Ser Asp Val Glu 1145 1150 1155 Tyr Glu Asn Gly ProGln Met Glu Phe Gln Lys Val Thr Thr Gly 1160 1165 1170 Ala Val Arg ProSer Asp Pro Pro Lys Trp Glu Arg Gly Met Glu 1175 1180 1185 Asn Ser IleSer Asp Ala Ser Arg Thr Ser Glu Tyr Lys Thr Glu 1190 1195 1200 Ile IleMet Lys Glu Asn Ser Ile Ser Asn Met Ser Leu Leu Arg 1205 1210 1215 AspSer Arg Asn Tyr Ser Gln Glu Thr Val Pro Lys Ala Ser Phe 1220 1225 1230Gly Phe Ser Gly Ile Ser Pro Leu Glu Asp Glu Ile Asn Lys Gly 1235 12401245 Ser Lys Ile Ser Gly Leu Gln Tyr Ser Ile Pro Asp Thr Glu Asn 12501255 1260 Gln Thr Leu Asn Tyr Gly Lys Thr Lys Glu Met Glu Lys Gln Asn1265 1270 1275 Thr Asp Lys Cys His Val Ser Ser His Thr Arg Leu Thr GluSer 1280 1285 1290 Ser Val His Asp Phe Lys Thr Glu Asp Gln Glu Val IleThr Thr 1295 1300 1305 Asp Phe Gly Gln Val Val Leu Arg Pro Lys Glu AlaArg His Ala 1310 1315 1320 Asn Val Asn Pro Asn Glu Asp Gly Glu Ser SerSer Ser Ser Pro 1325 1330 1335 Thr Glu Glu Asn Ala Ala Thr Asp Asn IleAla Phe Met Ile Thr 1340 1345 1350 Glu Thr Thr Val Gln Val Leu Ser SerGly Glu Val His Asp Ile 1355 1360 1365 Val Ser Gln Lys Gly Glu Asp IleGln Thr Val Asn Ile Asp Ala 1370 1375 1380 Arg Lys Glu Met Thr Pro ArgGln Glu Gly Thr Asp Asn Glu Asp 1385 1390 1395 Pro Val Val Cys Leu AspLys Lys Pro Val Ile Ile Ile Phe Asp 1400 1405 1410 Glu Pro Met Asp IleArg Ser Ala Tyr Lys Arg Leu Ser Thr Ile 1415 1420 1425 Phe Glu Glu CysAsp Glu Glu Leu Glu Arg Met Met Met Glu Glu 1430 1435 1440 Lys Ile GluGlu Glu Glu Glu Glu Glu Asn Gly Asp Ser Val Val 1445 1450 1455 Gln AsnAsn Asn Thr Ser Gln Met Ser His Lys Lys Val Ala Pro 1460 1465 1470 GlyAsn Leu Arg Thr Gly Gln Gln Val Glu Thr Lys Ser Gln Pro 1475 1480 1485His Ser Leu Ala Thr Glu Thr Arg Asn Pro Gly Gly Gln Glu Met 1490 14951500 Asn Arg Thr Glu Leu Asn Lys Phe Ser His Val Asp Ser Pro Asn 15051510 1515 Ser Glu Cys Lys Gly Glu Asp Ala Thr Asp Asp Gln Phe Glu Ser1520 1525 1530 Pro Lys Lys Lys Phe Lys Phe Lys Phe Pro Lys Lys Gln LeuAla 1535 1540 1545 Ala Leu Thr Gln Ala Ile Arg Thr Gly Thr Lys Thr GlyLys Lys 1550 1555 1560 Thr Leu Gln Val Val Val Tyr Glu Glu Glu Glu GluAsp Gly Thr 1565 1570 1575 Leu Lys Gln His Lys Glu Ala Lys Arg Phe GluIle Ala Arg Ser 1580 1585 1590 Gln Pro Glu Asp Thr Pro Glu Asn Thr ValArg Arg Gln Glu Gln 1595 1600 1605 Pro Ser Ile Glu Ser Thr Ser Pro IleSer Arg Thr Asp Glu Ile 1610 1615 1620 Arg Lys Asn Thr Tyr Arg Thr LeuAsp Ser Leu Glu Gln Thr Ile 1625 1630 1635 Lys Gln Leu Glu Asn Thr IleSer Glu Met Ser Pro Lys Ala Leu 1640 1645 1650 Val Asp Thr Ser Cys SerSer Asn Arg Asp Ser Val Ala Ser Ser 1655 1660 1665 Ser His Ile Ala GlnGlu Ala Ser Pro Arg Pro Leu Leu Val Pro 1670 1675 1680 Asp Glu Gly ProThr Ala Leu Glu Pro Pro Thr Ser Ile Pro Ser 1685 1690 1695 Ala Ser ArgLys Gly Ser Ser Gly Ala Pro Gln Thr Ser Arg Met 1700 1705 1710 Pro ValPro Met Ser Ala Lys Asn Arg Pro Gly Thr Leu Asp Lys 1715 1720 1725 ProGly Lys Gln Ser Lys Leu Gln Asp Pro Arg Gln Tyr Arg Gln 1730 1735 1740Ala Asn Gly Ser Ala Lys Lys Ser Gly Gly Asp Phe Lys Pro Thr 1745 17501755 Ser Pro Ser Leu Pro Ala Ser Lys Ile Pro Ala Leu Ser Pro Ser 17601765 1770 Ser Gly Lys Ser Ser Ser Leu Pro Ser Ser Ser Gly Asp Ser Ser1775 1780 1785 Asn Leu Pro Asn Pro Pro Ala Thr Lys Pro Ser Ile Ala SerAsn 1790 1795 1800 Pro Leu Ser Pro Gln Thr Gly Pro Pro Ala His Ser AlaSer Leu 1805 1810 1815 Ile Pro Ser Val Ser Asn Gly Ser Leu Lys Phe GlnSer Leu Thr 1820 1825 1830 His Thr Gly Lys Gly His His Leu Ser Phe SerPro Gln Ser Gln 1835 1840 1845 Asn Gly Arg Ala Pro Pro Pro Leu Ser PheSer Ser Ser Pro Pro 1850 1855 1860 Ser Pro Ala Ser Ser Val Ser Leu AsnGln Gly Ala Lys Gly Thr 1865 1870 1875 Arg Thr Ile His Thr Pro Ser LeuThr Ser Tyr Lys Ala Gln Asn 1880 1885 1890 Gly Ser Ser Ser Lys Ala ThrPro Ser Thr Ala Lys Glu Thr Ser 1895 1900 1905 16 5343 DNA Homo sapiensCDS (1)..(3927) 16 atg gaa gaa aat gaa agc cag aaa tgt gag ccg tgc cttcct tac tca 48 Met Glu Glu Asn Glu Ser Gln Lys Cys Glu Pro Cys Leu ProTyr Ser 1 5 10 15 gca gac aga aga cag atg cag gaa caa ggc aaa ggc aatctg cat gta 96 Ala Asp Arg Arg Gln Met Gln Glu Gln Gly Lys Gly Asn LeuHis Val 20 25 30 aca tca cca gaa gat gca gaa tgc cgc aga acc aag gaa cgcctt tct 144 Thr Ser Pro Glu Asp Ala Glu Cys Arg Arg Thr Lys Glu Arg LeuSer 35 40 45 aat gga aac agt cgt ggt tca gtt tcc aag tct tcc cgc aat atccca 192 Asn Gly Asn Ser Arg Gly Ser Val Ser Lys Ser Ser Arg Asn Ile Pro50 55 60 agg aga cac acc cta ggg ggg ccc cga agt tcc aag gaa ata ctg gga240 Arg Arg His Thr Leu Gly Gly Pro Arg Ser Ser Lys Glu Ile Leu Gly 6570 75 80 atg caa aca tct gag atg gat cgg aag aga gaa gcg ttc cta gaa cat288 Met Gln Thr Ser Glu Met Asp Arg Lys Arg Glu Ala Phe Leu Glu His 8590 95 ctg aag cag aag tac ccc cac cac gcc tct gca atc atg ggt cac caa336 Leu Lys Gln Lys Tyr Pro His His Ala Ser Ala Ile Met Gly His Gln 100105 110 gag agg ctg aga gac cag aca agg agc ccc aaa ctg tct cac agt cct384 Glu Arg Leu Arg Asp Gln Thr Arg Ser Pro Lys Leu Ser His Ser Pro 115120 125 caa cca ccc agt ctg ggt gac ccg gtc gag cat tta tca gag acg tcc432 Gln Pro Pro Ser Leu Gly Asp Pro Val Glu His Leu Ser Glu Thr Ser 130135 140 gct gat tct ttg gaa gcc atg tct gag ggg gat gct cca acc cct ttt480 Ala Asp Ser Leu Glu Ala Met Ser Glu Gly Asp Ala Pro Thr Pro Phe 145150 155 160 tcc aga ggc agc cgg act cgt gcg agc ctt cct gtg gtg agg tcaacc 528 Ser Arg Gly Ser Arg Thr Arg Ala Ser Leu Pro Val Val Arg Ser Thr165 170 175 aac cag acg aaa gaa aga tct ctg ggg gtt ctc tat ctc cag tatgga 576 Asn Gln Thr Lys Glu Arg Ser Leu Gly Val Leu Tyr Leu Gln Tyr Gly180 185 190 gat gaa acc aag cag ctc agg atg ccg aat gaa atc aca agt gcagac 624 Asp Glu Thr Lys Gln Leu Arg Met Pro Asn Glu Ile Thr Ser Ala Asp195 200 205 aca atc cgt gct ctc ttc gta agt gcc ttt cca cag cag ctc accatg 672 Thr Ile Arg Ala Leu Phe Val Ser Ala Phe Pro Gln Gln Leu Thr Met210 215 220 aaa atg ctg gaa tcg ccc agt gtc gcc att tac atc aaa gat gaaagc 720 Lys Met Leu Glu Ser Pro Ser Val Ala Ile Tyr Ile Lys Asp Glu Ser225 230 235 240 aga aat gtc tat tat gaa tta aat gat gta agg aac att caagac aga 768 Arg Asn Val Tyr Tyr Glu Leu Asn Asp Val Arg Asn Ile Gln AspArg 245 250 255 tca ctc ctc aaa gtg tac aac aag gat cct gca cat gcg tttaat cac 816 Ser Leu Leu Lys Val Tyr Asn Lys Asp Pro Ala His Ala Phe AsnHis 260 265 270 aca cca aaa act atg aat gga gac atg agg atg cag aga gaactt gtt 864 Thr Pro Lys Thr Met Asn Gly Asp Met Arg Met Gln Arg Glu LeuVal 275 280 285 tat gca aga gga gat ggc cct ggg gcc cct cgc ccc gga tctact gct 912 Tyr Ala Arg Gly Asp Gly Pro Gly Ala Pro Arg Pro Gly Ser ThrAla 290 295 300 cat cca ccc cat gcg att cca aat tcc cca ccg tct act ccagtg ccc 960 His Pro Pro His Ala Ile Pro Asn Ser Pro Pro Ser Thr Pro ValPro 305 310 315 320 cat tcc atg ccc ccc tcc ccg tcc aga att cct tat gggggc acc cgc 1008 His Ser Met Pro Pro Ser Pro Ser Arg Ile Pro Tyr Gly GlyThr Arg 325 330 335 tcc atg gtt gtt cct ggc aat gcc acc atc ccc agg gacaga atc tcc 1056 Ser Met Val Val Pro Gly Asn Ala Thr Ile Pro Arg Asp ArgIle Ser 340 345 350 agc ctg cca gtc tcc aga ccc atc tct cca agc cca agcgcc att tta 1104 Ser Leu Pro Val Ser Arg Pro Ile Ser Pro Ser Pro Ser AlaIle Leu 355 360 365 gaa aga aga gat gtc aag cct gat gaa gac atg agt ggcaaa aac att 1152 Glu Arg Arg Asp Val Lys Pro Asp Glu Asp Met Ser Gly LysAsn Ile 370 375 380 gca atg tac aga aat gag ggt ttc tat gct gat cct tacctt tat cac 1200 Ala Met Tyr Arg Asn Glu Gly Phe Tyr Ala Asp Pro Tyr LeuTyr His 385 390 395 400 gag gga cgg atg agc ata gcc tca tcc cat ggt ggacac cca ctg gat 1248 Glu Gly Arg Met Ser Ile Ala Ser Ser His Gly Gly HisPro Leu Asp 405 410 415 gtc ccc gac cac atc att gca tat cac cgc acc gccatc cgg tca gcg 1296 Val Pro Asp His Ile Ile Ala Tyr His Arg Thr Ala IleArg Ser Ala 420 425 430 agt gct tat tgt aac ccc tca atg caa gcg gaa atgcat atg gaa caa 1344 Ser Ala Tyr Cys Asn Pro Ser Met Gln Ala Glu Met HisMet Glu Gln 435 440 445 tca ctg tac aga cag aaa tca agg aaa tat ccg gatagc cat ttg cct 1392 Ser Leu Tyr Arg Gln Lys Ser Arg Lys Tyr Pro Asp SerHis Leu Pro 450 455 460 aca ctg ggc tcc aaa aca ccc cct gcc tct cct cacaga gtc agt gac 1440 Thr Leu Gly Ser Lys Thr Pro Pro Ala Ser Pro His ArgVal Ser Asp 465 470 475 480 ctg agg atg ata gac atg cac gct cac tat aatgcc cac ggc ccc cct 1488 Leu Arg Met Ile Asp Met His Ala His Tyr Asn AlaHis Gly Pro Pro 485 490 495 cac acc atg cag cca gac cgg gcc tct ccg agccgc cag gcc ttt aaa 1536 His Thr Met Gln Pro Asp Arg Ala Ser Pro Ser ArgGln Ala Phe Lys 500 505 510 aag gag cca ggc acc ttg gtg tat ata gaa aagcca cgg agc gct gca 1584 Lys Glu Pro Gly Thr Leu Val Tyr Ile Glu Lys ProArg Ser Ala Ala 515 520 525 gga tta tcc agc ctt gta gac ctc ggc cct cctcta atg gag aag caa 1632 Gly Leu Ser Ser Leu Val Asp Leu Gly Pro Pro LeuMet Glu Lys Gln 530 535 540 gtt ttt gcc tac agc acg gcg aca ata ccc aaagac aga gag acc agc 1680 Val Phe Ala Tyr Ser Thr Ala Thr Ile Pro Lys AspArg Glu Thr Ser 545 550 555 560 gag aaa atg atg aaa acc aca gcc aac aggaac cac aca gat agt gca 1728 Glu Lys Met Met Lys Thr Thr Ala Asn Arg AsnHis Thr Asp Ser Ala 565 570 575 gga acg ccc cat gtg tct ggt ggg aag atgctc agt gct ctg gag tcc 1776 Gly Thr Pro His Val Ser Gly Gly Lys Met LeuSer Ala Leu Glu Ser 580 585 590 acg gtg cct ccc agc cag cct cca cct gtgggc acc tca gcc atc cac 1824 Thr Val Pro Pro Ser Gln Pro Pro Pro Val GlyThr Ser Ala Ile His 595 600 605 atg agc ctg ctt gag atg agg cgg agc gtggcg gaa ctc agg ctc cag 1872 Met Ser Leu Leu Glu Met Arg Arg Ser Val AlaGlu Leu Arg Leu Gln 610 615 620 ctc cag cag atg cgg cag ctc cag ctg cagaac cag gag ttg ctg agg 1920 Leu Gln Gln Met Arg Gln Leu Gln Leu Gln AsnGln Glu Leu Leu Arg 625 630 635 640 gca atg atg aag aag gcc gag ctg gaaatc agt ggc aaa gtg atg gaa 1968 Ala Met Met Lys Lys Ala Glu Leu Glu IleSer Gly Lys Val Met Glu 645 650 655 aca atg aag aga ctg gag gat ccc gtgcag cga cag cgc gtc cta gtg 2016 Thr Met Lys Arg Leu Glu Asp Pro Val GlnArg Gln Arg Val Leu Val 660 665 670 gag caa gag aga caa aaa tat ctt catgag gaa gag aag atc gtc aag 2064 Glu Gln Glu Arg Gln Lys Tyr Leu His GluGlu Glu Lys Ile Val Lys 675 680 685 aag ttg tgc gag ttg gaa gac ttt gttgaa gac ttg aag aag gac tcc 2112 Lys Leu Cys Glu Leu Glu Asp Phe Val GluAsp Leu Lys Lys Asp Ser 690 695 700 acg gca gcc agc cga ttg gtt act ctgaaa gac gtg gaa gac ggg gct 2160 Thr Ala Ala Ser Arg Leu Val Thr Leu LysAsp Val Glu Asp Gly Ala 705 710 715 720 ttc ctc ctg cgt caa gtg gga gaggct gta gct acc ctg aaa gga gaa 2208 Phe Leu Leu Arg Gln Val Gly Glu AlaVal Ala Thr Leu Lys Gly Glu 725 730 735 ttt cca acc tta caa aac aag atgcga gcc atc ctg cgc ata gaa gtg 2256 Phe Pro Thr Leu Gln Asn Lys Met ArgAla Ile Leu Arg Ile Glu Val 740 745 750 gag gcc gtg cgg ttt ctg aag gaggag cca cac aag ctg gac agt ctc 2304 Glu Ala Val Arg Phe Leu Lys Glu GluPro His Lys Leu Asp Ser Leu 755 760 765 ctg aag cgt gtg cgc agc atg acagac gtc ctg acc atg ctg cgg aga 2352 Leu Lys Arg Val Arg Ser Met Thr AspVal Leu Thr Met Leu Arg Arg 770 775 780 cat gtc act gat ggg ctc ctg aaaggc acg gac gca gcc caa gcc gca 2400 His Val Thr Asp Gly Leu Leu Lys GlyThr Asp Ala Ala Gln Ala Ala 785 790 795 800 cag tac atg gct atg gaa aaggcc aca gcc gca gaa gtc ctg aag agt 2448 Gln Tyr Met Ala Met Glu Lys AlaThr Ala Ala Glu Val Leu Lys Ser 805 810 815 cag gag gag gca gcc cac acctcc ggc cag ccc ttc cac agc aca ggt 2496 Gln Glu Glu Ala Ala His Thr SerGly Gln Pro Phe His Ser Thr Gly 820 825 830 gcc cct ggc gat gcg aag tcggaa gtg gtg cct ttg tcc ggc atg atg 2544 Ala Pro Gly Asp Ala Lys Ser GluVal Val Pro Leu Ser Gly Met Met 835 840 845 gtt cgc cac gcg cag agc tcccct gtg gtc atc cag ccc tcc cag cac 2592 Val Arg His Ala Gln Ser Ser ProVal Val Ile Gln Pro Ser Gln His 850 855 860 tcc gtg gcc ctg ctg aac cctgct cag aac ttg cct cac gtg gcc agc 2640 Ser Val Ala Leu Leu Asn Pro AlaGln Asn Leu Pro His Val Ala Ser 865 870 875 880 tcc cca gcc gtc ccc caggaa gca acc tcc act ctg cag atg tcg cag 2688 Ser Pro Ala Val Pro Gln GluAla Thr Ser Thr Leu Gln Met Ser Gln 885 890 895 gct ccg cag tcc cca cagata ccc atg aat ggg tct gcc atg cag agc 2736 Ala Pro Gln Ser Pro Gln IlePro Met Asn Gly Ser Ala Met Gln Ser 900 905 910 ttg ttc att gaa gaa atccac agt gtg agt gcc aag aac agg gca gtg 2784 Leu Phe Ile Glu Glu Ile HisSer Val Ser Ala Lys Asn Arg Ala Val 915 920 925 tct atc gag aaa gca gaaaag aaa tgg gag gaa aaa agg caa aat ctg 2832 Ser Ile Glu Lys Ala Glu LysLys Trp Glu Glu Lys Arg Gln Asn Leu 930 935 940 gat cac tat aat ggg aaagag ttt gag aag ctc cta gaa gaa gct cag 2880 Asp His Tyr Asn Gly Lys GluPhe Glu Lys Leu Leu Glu Glu Ala Gln 945 950 955 960 gcc aat atc atg aagtca ata cca aat ctg gag atg ccg cca gcc aca 2928 Ala Asn Ile Met Lys SerIle Pro Asn Leu Glu Met Pro Pro Ala Thr 965 970 975 ggc cca ctg cca agggga gat gcc cca gtg gac aag gtg gaa ctt tca 2976 Gly Pro Leu Pro Arg GlyAsp Ala Pro Val Asp Lys Val Glu Leu Ser 980 985 990 gaa gat tct cca aattcg gaa cag gac ttg gaa aag ctg ggg gga aag 3024 Glu Asp Ser Pro Asn SerGlu Gln Asp Leu Glu Lys Leu Gly Gly Lys 995 1000 1005 tcg ccc cct cctcct ccg cca cct cct cgt cga agc tac ctg cca 3069 Ser Pro Pro Pro Pro ProPro Pro Pro Arg Arg Ser Tyr Leu Pro 1010 1015 1020 gga tcg gga ctc accacc acg agg tca ggc gat gtg gtc tac acc 3114 Gly Ser Gly Leu Thr Thr ThrArg Ser Gly Asp Val Val Tyr Thr 1025 1030 1035 ggc aga aag gag aac atcacc gct aag gca agc agt gaa gat gct 3159 Gly Arg Lys Glu Asn Ile Thr AlaLys Ala Ser Ser Glu Asp Ala 1040 1045 1050 gga cca agc cca cag acc agagct aca aaa tat cca gca gag gag 3204 Gly Pro Ser Pro Gln Thr Arg Ala ThrLys Tyr Pro Ala Glu Glu 1055 1060 1065 cct gct tca gcc tgg acc cca tcccca ccg cct gtc acc acc tcc 3249 Pro Ala Ser Ala Trp Thr Pro Ser Pro ProPro Val Thr Thr Ser 1070 1075 1080 tcc tca aag gat gag gag gaa gaa gaagaa gaa gga gac aaa ata 3294 Ser Ser Lys Asp Glu Glu Glu Glu Glu Glu GluGly Asp Lys Ile 1085 1090 1095 atg gca gaa ctc cag ggc tcc agc ggg gcccca cag acg agc agg 3339 Met Ala Glu Leu Gln Gly Ser Ser Gly Ala Pro GlnThr Ser Arg 1100 1105 1110 atg cct gtc ccc atg agt gcc aag aac aga cccgga acc ctg gac 3384 Met Pro Val Pro Met Ser Ala Lys Asn Arg Pro Gly ThrLeu Asp 1115 1120 1125 aaa ccc ggc aag cag tcc aaa ctg cag gat ccc cgccaa tat cgt 3429 Lys Pro Gly Lys Gln Ser Lys Leu Gln Asp Pro Arg Gln TyrArg 1130 1135 1140 cag gct aat gga agt gct aag aaa tct ggt ggg gac tttaag cct 3474 Gln Ala Asn Gly Ser Ala Lys Lys Ser Gly Gly Asp Phe Lys Pro1145 1150 1155 act tcc ccc tcc tta cct gct tct aag att cca gcc ctt tctccc 3519 Thr Ser Pro Ser Leu Pro Ala Ser Lys Ile Pro Ala Leu Ser Pro1160 1165 1170 agc tct ggg aaa agc agt tct ctg ccc tct tct agt ggt gacagc 3564 Ser Ser Gly Lys Ser Ser Ser Leu Pro Ser Ser Ser Gly Asp Ser1175 1180 1185 tct aac ctc cct aat cca cct gct act aaa cca tcg att gcttct 3609 Ser Asn Leu Pro Asn Pro Pro Ala Thr Lys Pro Ser Ile Ala Ser1190 1195 1200 aac cct ctc agc ccc caa aca gga cca cct gct cac tct gcctcc 3654 Asn Pro Leu Ser Pro Gln Thr Gly Pro Pro Ala His Ser Ala Ser1205 1210 1215 ctc atc cct tct gtc tct aat ggc tct ttg aag ttt cag agcctc 3699 Leu Ile Pro Ser Val Ser Asn Gly Ser Leu Lys Phe Gln Ser Leu1220 1225 1230 act cat aca ggt aaa ggt cac cat ctt tca ttc tca ccg cagagt 3744 Thr His Thr Gly Lys Gly His His Leu Ser Phe Ser Pro Gln Ser1235 1240 1245 caa aat ggc cga gca ccc cct cct ttg tca ttt tcc tcc tcccct 3789 Gln Asn Gly Arg Ala Pro Pro Pro Leu Ser Phe Ser Ser Ser Pro1250 1255 1260 cct tct cct gcc tcc tcc gtc tca ctg aat caa ggt gcc aagggc 3834 Pro Ser Pro Ala Ser Ser Val Ser Leu Asn Gln Gly Ala Lys Gly1265 1270 1275 acc agg acc atc cat act ccc agc ctc acc agc tac aag gcacag 3879 Thr Arg Thr Ile His Thr Pro Ser Leu Thr Ser Tyr Lys Ala Gln1280 1285 1290 aat gga agt tca agc aaa gcc acc cca tcc aca gca aaa gaaacc 3924 Asn Gly Ser Ser Ser Lys Ala Thr Pro Ser Thr Ala Lys Glu Thr1295 1300 1305 tct taaaggtcaa atcctattag gcacaagtcg gagttacatttaaaaaaaat 3977 Ser taacagtcta caacaactgt tttcacaaga gaatgtaacatattgctgta tcgtttgagg 4037 cttaatgcta aatatgtgct aaatactgga ttaatagatttcagtaaagc tcgttcgttt 4097 tgtttggttt tctttttacc tagttgctat agtgtctacagtctatactc aatacctata 4157 aaatgcagta agcatgtgtt acagaaagag gttctggtgggagagaaagg tgcgtgtgag 4217 acaggagaat tgtcttaagc atataaaaca tgtatgattccagaatttta gtatgttttg 4277 tataaaacta tttttcatta cggagactag aagtgaacagagaattacac aagtgtgact 4337 atacaaattg taaaacagat actataatat ttccttttattttagtgtta tttagcttta 4397 ttacagattt ctatttttgt caaaacttca tggttcctttcaagatcttt tttgccaaaa 4457 cattttgata ctatagcatt gtacatttga aagtagtgttctagactata aaaccaatga 4517 acttctacat gagccctaca gacaggcatg tgtagaaggcaatttatcaa acctattgca 4577 ctgccatgaa aagtgtgtat aataatttgc tagcccaagcaagctagttt tctttgcttg 4637 cttcttttct ttcttttttc cttccttttt tttttttttttcttttttaa catgttgaga 4697 ttctctagtt gttttctttg gcgtatctaa ccccttcttttgttttctga gacctggtaa 4757 cccacgctct tgcattgtgg attttaaaat gtatactctgtacggttctg taaaccgaaa 4817 aacttttgta aatatataaa tatacataga cataaaaatactgtatgtga cagcacatag 4877 agtagttttc ccacaccaaa gttaattttt atgcatgctttaaaagtata tatcgggacc 4937 ggcagaaatg gaagtatcca tacattttta aaaagcaacaagtttgcaca gctagagtgt 4997 ttttgtaaat aaatgtattt gtataacaca gtcatgtaatatacagaact ataagcagag 5057 actttgcaaa actaaataaa gggctgcatg cttattattttttgtacctt gtcactataa 5117 ctacttccta gtcaaagaac gaaatgtaac tgttaccgagttaaatgttt ttccgctttg 5177 agggatgtaa ccacatccac tcagaggaca ctacttttctgaaagctctg gggtgactaa 5237 tgatgagttc ctaataaatt aattgcaagt gtggtgccttggaaaaaaaa aaaaaaaaaa 5297 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaaaaaaaa 5343 17 1309 PRT Homo sapiens 17 Met Glu Glu Asn Glu Ser Gln LysCys Glu Pro Cys Leu Pro Tyr Ser 1 5 10 15 Ala Asp Arg Arg Gln Met GlnGlu Gln Gly Lys Gly Asn Leu His Val 20 25 30 Thr Ser Pro Glu Asp Ala GluCys Arg Arg Thr Lys Glu Arg Leu Ser 35 40 45 Asn Gly Asn Ser Arg Gly SerVal Ser Lys Ser Ser Arg Asn Ile Pro 50 55 60 Arg Arg His Thr Leu Gly GlyPro Arg Ser Ser Lys Glu Ile Leu Gly 65 70 75 80 Met Gln Thr Ser Glu MetAsp Arg Lys Arg Glu Ala Phe Leu Glu His 85 90 95 Leu Lys Gln Lys Tyr ProHis His Ala Ser Ala Ile Met Gly His Gln 100 105 110 Glu Arg Leu Arg AspGln Thr Arg Ser Pro Lys Leu Ser His Ser Pro 115 120 125 Gln Pro Pro SerLeu Gly Asp Pro Val Glu His Leu Ser Glu Thr Ser 130 135 140 Ala Asp SerLeu Glu Ala Met Ser Glu Gly Asp Ala Pro Thr Pro Phe 145 150 155 160 SerArg Gly Ser Arg Thr Arg Ala Ser Leu Pro Val Val Arg Ser Thr 165 170 175Asn Gln Thr Lys Glu Arg Ser Leu Gly Val Leu Tyr Leu Gln Tyr Gly 180 185190 Asp Glu Thr Lys Gln Leu Arg Met Pro Asn Glu Ile Thr Ser Ala Asp 195200 205 Thr Ile Arg Ala Leu Phe Val Ser Ala Phe Pro Gln Gln Leu Thr Met210 215 220 Lys Met Leu Glu Ser Pro Ser Val Ala Ile Tyr Ile Lys Asp GluSer 225 230 235 240 Arg Asn Val Tyr Tyr Glu Leu Asn Asp Val Arg Asn IleGln Asp Arg 245 250 255 Ser Leu Leu Lys Val Tyr Asn Lys Asp Pro Ala HisAla Phe Asn His 260 265 270 Thr Pro Lys Thr Met Asn Gly Asp Met Arg MetGln Arg Glu Leu Val 275 280 285 Tyr Ala Arg Gly Asp Gly Pro Gly Ala ProArg Pro Gly Ser Thr Ala 290 295 300 His Pro Pro His Ala Ile Pro Asn SerPro Pro Ser Thr Pro Val Pro 305 310 315 320 His Ser Met Pro Pro Ser ProSer Arg Ile Pro Tyr Gly Gly Thr Arg 325 330 335 Ser Met Val Val Pro GlyAsn Ala Thr Ile Pro Arg Asp Arg Ile Ser 340 345 350 Ser Leu Pro Val SerArg Pro Ile Ser Pro Ser Pro Ser Ala Ile Leu 355 360 365 Glu Arg Arg AspVal Lys Pro Asp Glu Asp Met Ser Gly Lys Asn Ile 370 375 380 Ala Met TyrArg Asn Glu Gly Phe Tyr Ala Asp Pro Tyr Leu Tyr His 385 390 395 400 GluGly Arg Met Ser Ile Ala Ser Ser His Gly Gly His Pro Leu Asp 405 410 415Val Pro Asp His Ile Ile Ala Tyr His Arg Thr Ala Ile Arg Ser Ala 420 425430 Ser Ala Tyr Cys Asn Pro Ser Met Gln Ala Glu Met His Met Glu Gln 435440 445 Ser Leu Tyr Arg Gln Lys Ser Arg Lys Tyr Pro Asp Ser His Leu Pro450 455 460 Thr Leu Gly Ser Lys Thr Pro Pro Ala Ser Pro His Arg Val SerAsp 465 470 475 480 Leu Arg Met Ile Asp Met His Ala His Tyr Asn Ala HisGly Pro Pro 485 490 495 His Thr Met Gln Pro Asp Arg Ala Ser Pro Ser ArgGln Ala Phe Lys 500 505 510 Lys Glu Pro Gly Thr Leu Val Tyr Ile Glu LysPro Arg Ser Ala Ala 515 520 525 Gly Leu Ser Ser Leu Val Asp Leu Gly ProPro Leu Met Glu Lys Gln 530 535 540 Val Phe Ala Tyr Ser Thr Ala Thr IlePro Lys Asp Arg Glu Thr Ser 545 550 555 560 Glu Lys Met Met Lys Thr ThrAla Asn Arg Asn His Thr Asp Ser Ala 565 570 575 Gly Thr Pro His Val SerGly Gly Lys Met Leu Ser Ala Leu Glu Ser 580 585 590 Thr Val Pro Pro SerGln Pro Pro Pro Val Gly Thr Ser Ala Ile His 595 600 605 Met Ser Leu LeuGlu Met Arg Arg Ser Val Ala Glu Leu Arg Leu Gln 610 615 620 Leu Gln GlnMet Arg Gln Leu Gln Leu Gln Asn Gln Glu Leu Leu Arg 625 630 635 640 AlaMet Met Lys Lys Ala Glu Leu Glu Ile Ser Gly Lys Val Met Glu 645 650 655Thr Met Lys Arg Leu Glu Asp Pro Val Gln Arg Gln Arg Val Leu Val 660 665670 Glu Gln Glu Arg Gln Lys Tyr Leu His Glu Glu Glu Lys Ile Val Lys 675680 685 Lys Leu Cys Glu Leu Glu Asp Phe Val Glu Asp Leu Lys Lys Asp Ser690 695 700 Thr Ala Ala Ser Arg Leu Val Thr Leu Lys Asp Val Glu Asp GlyAla 705 710 715 720 Phe Leu Leu Arg Gln Val Gly Glu Ala Val Ala Thr LeuLys Gly Glu 725 730 735 Phe Pro Thr Leu Gln Asn Lys Met Arg Ala Ile LeuArg Ile Glu Val 740 745 750 Glu Ala Val Arg Phe Leu Lys Glu Glu Pro HisLys Leu Asp Ser Leu 755 760 765 Leu Lys Arg Val Arg Ser Met Thr Asp ValLeu Thr Met Leu Arg Arg 770 775 780 His Val Thr Asp Gly Leu Leu Lys GlyThr Asp Ala Ala Gln Ala Ala 785 790 795 800 Gln Tyr Met Ala Met Glu LysAla Thr Ala Ala Glu Val Leu Lys Ser 805 810 815 Gln Glu Glu Ala Ala HisThr Ser Gly Gln Pro Phe His Ser Thr Gly 820 825 830 Ala Pro Gly Asp AlaLys Ser Glu Val Val Pro Leu Ser Gly Met Met 835 840 845 Val Arg His AlaGln Ser Ser Pro Val Val Ile Gln Pro Ser Gln His 850 855 860 Ser Val AlaLeu Leu Asn Pro Ala Gln Asn Leu Pro His Val Ala Ser 865 870 875 880 SerPro Ala Val Pro Gln Glu Ala Thr Ser Thr Leu Gln Met Ser Gln 885 890 895Ala Pro Gln Ser Pro Gln Ile Pro Met Asn Gly Ser Ala Met Gln Ser 900 905910 Leu Phe Ile Glu Glu Ile His Ser Val Ser Ala Lys Asn Arg Ala Val 915920 925 Ser Ile Glu Lys Ala Glu Lys Lys Trp Glu Glu Lys Arg Gln Asn Leu930 935 940 Asp His Tyr Asn Gly Lys Glu Phe Glu Lys Leu Leu Glu Glu AlaGln 945 950 955 960 Ala Asn Ile Met Lys Ser Ile Pro Asn Leu Glu Met ProPro Ala Thr 965 970 975 Gly Pro Leu Pro Arg Gly Asp Ala Pro Val Asp LysVal Glu Leu Ser 980 985 990 Glu Asp Ser Pro Asn Ser Glu Gln Asp Leu GluLys Leu Gly Gly Lys 995 1000 1005 Ser Pro Pro Pro Pro Pro Pro Pro ProArg Arg Ser Tyr Leu Pro 1010 1015 1020 Gly Ser Gly Leu Thr Thr Thr ArgSer Gly Asp Val Val Tyr Thr 1025 1030 1035 Gly Arg Lys Glu Asn Ile ThrAla Lys Ala Ser Ser Glu Asp Ala 1040 1045 1050 Gly Pro Ser Pro Gln ThrArg Ala Thr Lys Tyr Pro Ala Glu Glu 1055 1060 1065 Pro Ala Ser Ala TrpThr Pro Ser Pro Pro Pro Val Thr Thr Ser 1070 1075 1080 Ser Ser Lys AspGlu Glu Glu Glu Glu Glu Glu Gly Asp Lys Ile 1085 1090 1095 Met Ala GluLeu Gln Gly Ser Ser Gly Ala Pro Gln Thr Ser Arg 1100 1105 1110 Met ProVal Pro Met Ser Ala Lys Asn Arg Pro Gly Thr Leu Asp 1115 1120 1125 LysPro Gly Lys Gln Ser Lys Leu Gln Asp Pro Arg Gln Tyr Arg 1130 1135 1140Gln Ala Asn Gly Ser Ala Lys Lys Ser Gly Gly Asp Phe Lys Pro 1145 11501155 Thr Ser Pro Ser Leu Pro Ala Ser Lys Ile Pro Ala Leu Ser Pro 11601165 1170 Ser Ser Gly Lys Ser Ser Ser Leu Pro Ser Ser Ser Gly Asp Ser1175 1180 1185 Ser Asn Leu Pro Asn Pro Pro Ala Thr Lys Pro Ser Ile AlaSer 1190 1195 1200 Asn Pro Leu Ser Pro Gln Thr Gly Pro Pro Ala His SerAla Ser 1205 1210 1215 Leu Ile Pro Ser Val Ser Asn Gly Ser Leu Lys PheGln Ser Leu 1220 1225 1230 Thr His Thr Gly Lys Gly His His Leu Ser PheSer Pro Gln Ser 1235 1240 1245 Gln Asn Gly Arg Ala Pro Pro Pro Leu SerPhe Ser Ser Ser Pro 1250 1255 1260 Pro Ser Pro Ala Ser Ser Val Ser LeuAsn Gln Gly Ala Lys Gly 1265 1270 1275 Thr Arg Thr Ile His Thr Pro SerLeu Thr Ser Tyr Lys Ala Gln 1280 1285 1290 Asn Gly Ser Ser Ser Lys AlaThr Pro Ser Thr Ala Lys Glu Thr 1295 1300 1305 Ser 18 5196 DNA Homosapiens CDS (12)..(4790) 18 gtgagaggaa g atg gcg gcc gcg gct gtg gtg gttccc gca gag tgg ata 50 Met Ala Ala Ala Ala Val Val Val Pro Ala Glu TrpIle 1 5 10 aag aac tgg gag aaa tca ggg aga ggc gaa ttt ttg cat tta tgtcgg 98 Lys Asn Trp Glu Lys Ser Gly Arg Gly Glu Phe Leu His Leu Cys Arg15 20 25 atc ctc agt gaa aat aaa agc cat gat agt tca aca tac aga gat ttc146 Ile Leu Ser Glu Asn Lys Ser His Asp Ser Ser Thr Tyr Arg Asp Phe 3035 40 45 cag caa gct ctc tat gag ttg tca tat cat gta att aaa gga aat cta194 Gln Gln Ala Leu Tyr Glu Leu Ser Tyr His Val Ile Lys Gly Asn Leu 5055 60 aag cat gaa cag gca tct aat gtt ctt agt gac att agt gaa ttt cgt242 Lys His Glu Gln Ala Ser Asn Val Leu Ser Asp Ile Ser Glu Phe Arg 6570 75 gag gat atg ccc tcc att ctt gct gat gta ttc tgc ata tta gac att290 Glu Asp Met Pro Ser Ile Leu Ala Asp Val Phe Cys Ile Leu Asp Ile 8085 90 gag aca aat tgt tta gaa gaa aaa agc aag aga gac tat ttt aca cag338 Glu Thr Asn Cys Leu Glu Glu Lys Ser Lys Arg Asp Tyr Phe Thr Gln 95100 105 ttg gta tta gca tgt ttg tat tta gtt tca gac aca gtt cta aag gaa386 Leu Val Leu Ala Cys Leu Tyr Leu Val Ser Asp Thr Val Leu Lys Glu 110115 120 125 cgc ctg gat cca gaa aca ctg gaa tca tta ggg ctt atc aaa caatca 434 Arg Leu Asp Pro Glu Thr Leu Glu Ser Leu Gly Leu Ile Lys Gln Ser130 135 140 cag caa ttc aat caa aag tca gtt aaa atc aag aca aaa ctc ttttat 482 Gln Gln Phe Asn Gln Lys Ser Val Lys Ile Lys Thr Lys Leu Phe Tyr145 150 155 aag cag caa aaa ttc aat ttg tta aga gaa gag aat gaa ggt tatgcc 530 Lys Gln Gln Lys Phe Asn Leu Leu Arg Glu Glu Asn Glu Gly Tyr Ala160 165 170 aag ctg att gct gaa ttg ggg caa gat tta tct gga agt att actagt 578 Lys Leu Ile Ala Glu Leu Gly Gln Asp Leu Ser Gly Ser Ile Thr Ser175 180 185 gat tta atc tta gaa aat atc aaa tct tta ata gga tgc ttt aatctg 626 Asp Leu Ile Leu Glu Asn Ile Lys Ser Leu Ile Gly Cys Phe Asn Leu190 195 200 205 gat ccc aat aga gtt ttg gat gtc att tta gaa gtg ttt gaatgc agg 674 Asp Pro Asn Arg Val Leu Asp Val Ile Leu Glu Val Phe Glu CysArg 210 215 220 cca gaa cac gat gac ttc ttt ata tct ttg tta gaa tct tacatg agt 722 Pro Glu His Asp Asp Phe Phe Ile Ser Leu Leu Glu Ser Tyr MetSer 225 230 235 atg tgt gaa ccg caa aca ctg tgt cat att ctt ggg ttc aaattc aag 770 Met Cys Glu Pro Gln Thr Leu Cys His Ile Leu Gly Phe Lys PheLys 240 245 250 ttt tac cag gaa cca aat ggc gag aca cca tca tct tta tacaga gtt 818 Phe Tyr Gln Glu Pro Asn Gly Glu Thr Pro Ser Ser Leu Tyr ArgVal 255 260 265 gca gca gta ctt cta caa ttt aat ctt att gat tta gat gatctt tat 866 Ala Ala Val Leu Leu Gln Phe Asn Leu Ile Asp Leu Asp Asp LeuTyr 270 275 280 285 gta cat ctt ctt ccg gct gat aat tgc att atg gat gaacac aaa cga 914 Val His Leu Leu Pro Ala Asp Asn Cys Ile Met Asp Glu HisLys Arg 290 295 300 gaa att gcg gaa gct aag caa att gtt aga aag ctt acgatg gtt gtg 962 Glu Ile Ala Glu Ala Lys Gln Ile Val Arg Lys Leu Thr MetVal Val 305 310 315 ttg tct tct gaa aaa atg gat gag cga gag aaa gaa aaggaa aaa gaa 1010 Leu Ser Ser Glu Lys Met Asp Glu Arg Glu Lys Glu Lys GluLys Glu 320 325 330 gag gag aaa gta gag aaa cca cct gat aac caa aaa cttggc ttg ttg 1058 Glu Glu Lys Val Glu Lys Pro Pro Asp Asn Gln Lys Leu GlyLeu Leu 335 340 345 gaa gcc tta tta aag att ggt gat tgg caa cat gca cagaac att atg 1106 Glu Ala Leu Leu Lys Ile Gly Asp Trp Gln His Ala Gln AsnIle Met 350 355 360 365 gat cag atg cct cca tac tat gca gct tca cac aagcta ata gcc ctt 1154 Asp Gln Met Pro Pro Tyr Tyr Ala Ala Ser His Lys LeuIle Ala Leu 370 375 380 gct att tgc aag ctc att cat ata act att gag cctctc tac cga aga 1202 Ala Ile Cys Lys Leu Ile His Ile Thr Ile Glu Pro LeuTyr Arg Arg 385 390 395 gtt gga gtt cct aaa ggt gct aaa ggc tca cct gttaat gct ttg caa 1250 Val Gly Val Pro Lys Gly Ala Lys Gly Ser Pro Val AsnAla Leu Gln 400 405 410 aac aag aga gca cca aaa caa gct gag agc ttt gaagat ttg agg aga 1298 Asn Lys Arg Ala Pro Lys Gln Ala Glu Ser Phe Glu AspLeu Arg Arg 415 420 425 gac gtg ttc aat atg ttc tgt tac ctt ggt cct cacctt tct cac gat 1346 Asp Val Phe Asn Met Phe Cys Tyr Leu Gly Pro His LeuSer His Asp 430 435 440 445 ccc att tta ttt gca aaa gtg gtg cgc ata ggcaag tca ttt atg aag 1394 Pro Ile Leu Phe Ala Lys Val Val Arg Ile Gly LysSer Phe Met Lys 450 455 460 gag ttt cag tct gat gga agc aaa caa gaa gataaa gaa aaa acg gaa 1442 Glu Phe Gln Ser Asp Gly Ser Lys Gln Glu Asp LysGlu Lys Thr Glu 465 470 475 gtt atc ctt agc tgt ttg ctt agc att act gaccag gta cta ctt cca 1490 Val Ile Leu Ser Cys Leu Leu Ser Ile Thr Asp GlnVal Leu Leu Pro 480 485 490 tct ctt tct ttg atg gac tgc aat gct tgt atgtct gag gaa cta tgg 1538 Ser Leu Ser Leu Met Asp Cys Asn Ala Cys Met SerGlu Glu Leu Trp 495 500 505 gga atg ttt aaa aca ttt cca tat cag cat agatat cgt ctg tat ggc 1586 Gly Met Phe Lys Thr Phe Pro Tyr Gln His Arg TyrArg Leu Tyr Gly 510 515 520 525 cag tgg aag aat gaa act tat aac agt caccca ctt tta gta aaa gtt 1634 Gln Trp Lys Asn Glu Thr Tyr Asn Ser His ProLeu Leu Val Lys Val 530 535 540 aaa gct caa aca ata gac aga gcc aaa tatatc atg aag cgc cta acc 1682 Lys Ala Gln Thr Ile Asp Arg Ala Lys Tyr IleMet Lys Arg Leu Thr 545 550 555 aag gaa aat gtg aag cct tct gga aga caaatt ggg aag ttg agc cac 1730 Lys Glu Asn Val Lys Pro Ser Gly Arg Gln IleGly Lys Leu Ser His 560 565 570 agc aat cca acc att ttg ttt gat tat atcttg tca caa ata cag aag 1778 Ser Asn Pro Thr Ile Leu Phe Asp Tyr Ile LeuSer Gln Ile Gln Lys 575 580 585 tat gat aac tta ata aca cct gta gta gattca ttg aaa tac ctc act 1826 Tyr Asp Asn Leu Ile Thr Pro Val Val Asp SerLeu Lys Tyr Leu Thr 590 595 600 605 tca ctg aat tat gat gtc ttg gcc tattgt atc att gaa gct tta gct 1874 Ser Leu Asn Tyr Asp Val Leu Ala Tyr CysIle Ile Glu Ala Leu Ala 610 615 620 aat cca gaa aag gaa aga atg aaa catgat gac aca acc atc tca agc 1922 Asn Pro Glu Lys Glu Arg Met Lys His AspAsp Thr Thr Ile Ser Ser 625 630 635 tgg ctt cag agt ctg gct agt ttc tgtggt gca gtt ttt cgt aaa tat 1970 Trp Leu Gln Ser Leu Ala Ser Phe Cys GlyAla Val Phe Arg Lys Tyr 640 645 650 cca att gat ctt gct ggt ctt ctt cagtat gtt gcc aat cag cta aag 2018 Pro Ile Asp Leu Ala Gly Leu Leu Gln TyrVal Ala Asn Gln Leu Lys 655 660 665 gcg ggc aaa agt ttt gac ctg ctt atattg aaa gaa gtg gta caa aaa 2066 Ala Gly Lys Ser Phe Asp Leu Leu Ile LeuLys Glu Val Val Gln Lys 670 675 680 685 atg gca gga ata gaa att aca gaggaa atg aca atg gag caa cta gag 2114 Met Ala Gly Ile Glu Ile Thr Glu GluMet Thr Met Glu Gln Leu Glu 690 695 700 gct atg act ggt gga gag cag ctaaaa gct gag ggt ggt tat ttt ggt 2162 Ala Met Thr Gly Gly Glu Gln Leu LysAla Glu Gly Gly Tyr Phe Gly 705 710 715 cag atc aga aac act aaa aaa tcctct cag aga tta aag gat gct cta 2210 Gln Ile Arg Asn Thr Lys Lys Ser SerGln Arg Leu Lys Asp Ala Leu 720 725 730 ttg gac cat gat ctt gcc ctt cctctc tgt ctg ctt atg gct cag cag 2258 Leu Asp His Asp Leu Ala Leu Pro LeuCys Leu Leu Met Ala Gln Gln 735 740 745 aga aat ggg gta atc ttt cag gaaggt gga gag aaa cat ttg aaa ctt 2306 Arg Asn Gly Val Ile Phe Gln Glu GlyGly Glu Lys His Leu Lys Leu 750 755 760 765 gtg gga aag ctc tat gac cagtgt cat gat acc ctg gtg cag ttt ggt 2354 Val Gly Lys Leu Tyr Asp Gln CysHis Asp Thr Leu Val Gln Phe Gly 770 775 780 ggg ttt tta gca tct aat ctgagc aca gaa gat tat ata aag cga gtg 2402 Gly Phe Leu Ala Ser Asn Leu SerThr Glu Asp Tyr Ile Lys Arg Val 785 790 795 cct tca att gat gta ctc tgtaat gaa ttt cat aca ccc cat gat gca 2450 Pro Ser Ile Asp Val Leu Cys AsnGlu Phe His Thr Pro His Asp Ala 800 805 810 gca ttt ttc ctg tct agg ccaatg tat gcc cat cat att tcg tca aag 2498 Ala Phe Phe Leu Ser Arg Pro MetTyr Ala His His Ile Ser Ser Lys 815 820 825 tat gat gaa ctt aaa aaa tcagaa aag gga agt aaa cag caa cat aaa 2546 Tyr Asp Glu Leu Lys Lys Ser GluLys Gly Ser Lys Gln Gln His Lys 830 835 840 845 gtt cat aag tac att acatca tgt gag atg gtg atg gcg cct gtc cat 2594 Val His Lys Tyr Ile Thr SerCys Glu Met Val Met Ala Pro Val His 850 855 860 gaa gca gtg gtc tcc ttacat gtt tcc aaa gtc tgg gat gac atc agc 2642 Glu Ala Val Val Ser Leu HisVal Ser Lys Val Trp Asp Asp Ile Ser 865 870 875 cct caa ttc tat gct acattc tgg tca ttg aca atg tat gac ctt gca 2690 Pro Gln Phe Tyr Ala Thr PheTrp Ser Leu Thr Met Tyr Asp Leu Ala 880 885 890 gtt cca cac acc agc tatgaa cga gaa gtc aat aaa ctt aaa gtc cag 2738 Val Pro His Thr Ser Tyr GluArg Glu Val Asn Lys Leu Lys Val Gln 895 900 905 atg aaa gca att gat gacaat cag gaa atg ccc cca aat aaa aag aaa 2786 Met Lys Ala Ile Asp Asp AsnGln Glu Met Pro Pro Asn Lys Lys Lys 910 915 920 925 aaa gag aag gag cgctgt act gcc ctt cag gac aag ctt ctt gaa gaa 2834 Lys Glu Lys Glu Arg CysThr Ala Leu Gln Asp Lys Leu Leu Glu Glu 930 935 940 gaa aag aaa cag atggaa cat gta cag aga gtt cta cag aga ttg aaa 2882 Glu Lys Lys Gln Met GluHis Val Gln Arg Val Leu Gln Arg Leu Lys 945 950 955 ctg gaa aag gac aactgg ctt tta gca aaa tct acc aaa aat gag acc 2930 Leu Glu Lys Asp Asn TrpLeu Leu Ala Lys Ser Thr Lys Asn Glu Thr 960 965 970 atc aca aaa ttt ctacag ctg tgt ata ttt cct cga tgt att ttt tca 2978 Ile Thr Lys Phe Leu GlnLeu Cys Ile Phe Pro Arg Cys Ile Phe Ser 975 980 985 gca att gat gct gtttac tgt gct cgt ttt gtt gaa ttg gta cat caa 3026 Ala Ile Asp Ala Val TyrCys Ala Arg Phe Val Glu Leu Val His Gln 990 995 1000 1005 cag aaa actcca aat ttt tcc aca ctt ctt tgc tat gat cga gtt 3071 Gln Lys Thr Pro AsnPhe Ser Thr Leu Leu Cys Tyr Asp Arg Val 1010 1015 1020 ttc tct gac ataatt tac aca gtt gca agc tgt act gaa aat gaa 3116 Phe Ser Asp Ile Ile TyrThr Val Ala Ser Cys Thr Glu Asn Glu 1025 1030 1035 gcc agt cga tac ggaagg ttt ctt tgc tgc atg tta gag act gtg 3161 Ala Ser Arg Tyr Gly Arg PheLeu Cys Cys Met Leu Glu Thr Val 1040 1045 1050 acc agg tgg cat agt gataga gcc aca tat gaa aag gaa tgt gga 3206 Thr Arg Trp His Ser Asp Arg AlaThr Tyr Glu Lys Glu Cys Gly 1055 1060 1065 aac tat cca gga ttc ctt accata tta cgg gca act gga ttt gat 3251 Asn Tyr Pro Gly Phe Leu Thr Ile LeuArg Ala Thr Gly Phe Asp 1070 1075 1080 ggt gga aat aag gct gat caa ttagac tat gaa aat ttt cga cat 3296 Gly Gly Asn Lys Ala Asp Gln Leu Asp TyrGlu Asn Phe Arg His 1085 1090 1095 gtt gta cat aaa tgg cat tac aaa ctaacc aag gca tcg gta cat 3341 Val Val His Lys Trp His Tyr Lys Leu Thr LysAla Ser Val His 1100 1105 1110 tgc ctt gaa aca ggc gaa tat act cac atcagg aat atc ttg att 3386 Cys Leu Glu Thr Gly Glu Tyr Thr His Ile Arg AsnIle Leu Ile 1115 1120 1125 gtg cta aca aaa ata ctt cct tgg tac cca aaagtt ttg aat ctg 3431 Val Leu Thr Lys Ile Leu Pro Trp Tyr Pro Lys Val LeuAsn Leu 1130 1135 1140 ggt caa gct ttg gaa aga aga gta cac aaa atc tgccaa gaa gaa 3476 Gly Gln Ala Leu Glu Arg Arg Val His Lys Ile Cys Gln GluGlu 1145 1150 1155 aaa gag aag agg cca gat cta tat gca ttg gct atg ggctac tct 3521 Lys Glu Lys Arg Pro Asp Leu Tyr Ala Leu Ala Met Gly Tyr Ser1160 1165 1170 ggg cag ttg aaa agt aga aag tca tac atg ata cct gaa aatgag 3566 Gly Gln Leu Lys Ser Arg Lys Ser Tyr Met Ile Pro Glu Asn Glu1175 1180 1185 ttt cat cac aaa gac ccc cct ccg agg aat gca gtt gcc agtgtg 3611 Phe His His Lys Asp Pro Pro Pro Arg Asn Ala Val Ala Ser Val1190 1195 1200 caa aat ggg cct ggt ggt ggg cct tct tca tca tca ata ggaagt 3656 Gln Asn Gly Pro Gly Gly Gly Pro Ser Ser Ser Ser Ile Gly Ser1205 1210 1215 gca tct aaa tcg gat gaa agc agt act gag gag act gat aaatca 3701 Ala Ser Lys Ser Asp Glu Ser Ser Thr Glu Glu Thr Asp Lys Ser1220 1225 1230 agg gag aga tct cag tgt ggt gtg aaa gct gtt aat aaa gcttct 3746 Arg Glu Arg Ser Gln Cys Gly Val Lys Ala Val Asn Lys Ala Ser1235 1240 1245 agt acc aca cct aaa ggg aat tca agc aat gga aat agt ggctct 3791 Ser Thr Thr Pro Lys Gly Asn Ser Ser Asn Gly Asn Ser Gly Ser1250 1255 1260 aac agc aac aaa gct gtt aaa gaa aat gac aaa gaa aaa gggaaa 3836 Asn Ser Asn Lys Ala Val Lys Glu Asn Asp Lys Glu Lys Gly Lys1265 1270 1275 gag aaa gaa aaa gag aaa aaa gaa aag act cca gct act actcca 3881 Glu Lys Glu Lys Glu Lys Lys Glu Lys Thr Pro Ala Thr Thr Pro1280 1285 1290 gag gcc agg gta ctt ggt aaa gat ggt aaa gaa aaa cca aaggaa 3926 Glu Ala Arg Val Leu Gly Lys Asp Gly Lys Glu Lys Pro Lys Glu1295 1300 1305 gag cgg cca aat aaa gat gaa aaa gca aga gag acc aag gaaaga 3971 Glu Arg Pro Asn Lys Asp Glu Lys Ala Arg Glu Thr Lys Glu Arg1310 1315 1320 acg ccg aag tct gac aaa gag aaa gaa aaa ttc aag aag gaagaa 4016 Thr Pro Lys Ser Asp Lys Glu Lys Glu Lys Phe Lys Lys Glu Glu1325 1330 1335 aaa gct aaa gat gag aaa ttt aag acc act gtc ccc aac gcagaa 4061 Lys Ala Lys Asp Glu Lys Phe Lys Thr Thr Val Pro Asn Ala Glu1340 1345 1350 tca aaa tca act caa gaa agg gaa aga gag aag gag cca tccaga 4106 Ser Lys Ser Thr Gln Glu Arg Glu Arg Glu Lys Glu Pro Ser Arg1355 1360 1365 gaa aga gat ata gca aag gaa atg aaa tca aag gaa aat gttaaa 4151 Glu Arg Asp Ile Ala Lys Glu Met Lys Ser Lys Glu Asn Val Lys1370 1375 1380 gga gga gaa aaa aca cca gtt tct ggg tcc ttg aaa tca cctgtt 4196 Gly Gly Glu Lys Thr Pro Val Ser Gly Ser Leu Lys Ser Pro Val1385 1390 1395 ccc aga tca gat att cca gag cct gaa agg gaa caa aaa cgccgc 4241 Pro Arg Ser Asp Ile Pro Glu Pro Glu Arg Glu Gln Lys Arg Arg1400 1405 1410 aaa att gat act cac cct tct cca tca cat tcc tcc aca gtaaag 4286 Lys Ile Asp Thr His Pro Ser Pro Ser His Ser Ser Thr Val Lys1415 1420 1425 gac agt ctc atc gaa ctc aag gaa tct tca gca aag ctc tacatt 4331 Asp Ser Leu Ile Glu Leu Lys Glu Ser Ser Ala Lys Leu Tyr Ile1430 1435 1440 aat cat act cct cca cca ctg tcc aag agt aag gag aga gaaatg 4376 Asn His Thr Pro Pro Pro Leu Ser Lys Ser Lys Glu Arg Glu Met1445 1450 1455 gac aag aaa gat ttg gac aag tca agg gaa aga tcc aga gaaaga 4421 Asp Lys Lys Asp Leu Asp Lys Ser Arg Glu Arg Ser Arg Glu Arg1460 1465 1470 gag aaa aaa gat gaa aag gac agg aaa gag cgg aaa agg gatcac 4466 Glu Lys Lys Asp Glu Lys Asp Arg Lys Glu Arg Lys Arg Asp His1475 1480 1485 tca aac aac gac cgt gaa gtg cca ccg gac tta acc aag agacgt 4511 Ser Asn Asn Asp Arg Glu Val Pro Pro Asp Leu Thr Lys Arg Arg1490 1495 1500 aaa gag gag aat gga aca atg ggg gtt tca aaa cat aaa agtgaa 4556 Lys Glu Glu Asn Gly Thr Met Gly Val Ser Lys His Lys Ser Glu1505 1510 1515 agt cct tgt gaa tct cct tat cca aat gag aaa gac aag gaaaaa 4601 Ser Pro Cys Glu Ser Pro Tyr Pro Asn Glu Lys Asp Lys Glu Lys1520 1525 1530 aat aag tca aaa tct tca ggc aaa gaa aaa ggc agt gat tcattt 4646 Asn Lys Ser Lys Ser Ser Gly Lys Glu Lys Gly Ser Asp Ser Phe1535 1540 1545 aaa tct gag aag atg gat aaa atc tcc tcc ggt ggc aaa aaggag 4691 Lys Ser Glu Lys Met Asp Lys Ile Ser Ser Gly Gly Lys Lys Glu1550 1555 1560 tcc agg cat gat aaa gaa aag ata gaa aag aaa gag aaa cgggac 4736 Ser Arg His Asp Lys Glu Lys Ile Glu Lys Lys Glu Lys Arg Asp1565 1570 1575 agt tca gga gga aag gaa gag aag aaa cat cat aag tcc tcggac 4781 Ser Ser Gly Gly Lys Glu Glu Lys Lys His His Lys Ser Ser Asp1580 1585 1590 aag cac aga taatgaagac tttccatcaa ggtgagatcg gactggaact4830 Lys His Arg gttcggctgc gaccagaaat ttattttcct gagtaaattg ccgagaattaagaatgaaga 4890 gggccatttg catctcctta aattattcag ttacctgctt tattgctccatgtggaaaac 4950 ttaaaattgt taagttgtgc attactgtat tttaacttgt tgcttagtttctacatgttt 5010 attttcagta atggctgaaa gtgttaactg ttccatactt ttagcacaatgtgctgcata 5070 aggttacctg tgtacagagt tttactttag attaactaaa tattgcctgggttcagtttt 5130 tatttccatt ctgaaatgct tcctttttat tgtttgaaac tgaaaataaacaattgttga 5190 accctt 5196 19 1593 PRT Homo sapiens 19 Met Ala Ala AlaAla Val Val Val Pro Ala Glu Trp Ile Lys Asn Trp 1 5 10 15 Glu Lys SerGly Arg Gly Glu Phe Leu His Leu Cys Arg Ile Leu Ser 20 25 30 Glu Asn LysSer His Asp Ser Ser Thr Tyr Arg Asp Phe Gln Gln Ala 35 40 45 Leu Tyr GluLeu Ser Tyr His Val Ile Lys Gly Asn Leu Lys His Glu 50 55 60 Gln Ala SerAsn Val Leu Ser Asp Ile Ser Glu Phe Arg Glu Asp Met 65 70 75 80 Pro SerIle Leu Ala Asp Val Phe Cys Ile Leu Asp Ile Glu Thr Asn 85 90 95 Cys LeuGlu Glu Lys Ser Lys Arg Asp Tyr Phe Thr Gln Leu Val Leu 100 105 110 AlaCys Leu Tyr Leu Val Ser Asp Thr Val Leu Lys Glu Arg Leu Asp 115 120 125Pro Glu Thr Leu Glu Ser Leu Gly Leu Ile Lys Gln Ser Gln Gln Phe 130 135140 Asn Gln Lys Ser Val Lys Ile Lys Thr Lys Leu Phe Tyr Lys Gln Gln 145150 155 160 Lys Phe Asn Leu Leu Arg Glu Glu Asn Glu Gly Tyr Ala Lys LeuIle 165 170 175 Ala Glu Leu Gly Gln Asp Leu Ser Gly Ser Ile Thr Ser AspLeu Ile 180 185 190 Leu Glu Asn Ile Lys Ser Leu Ile Gly Cys Phe Asn LeuAsp Pro Asn 195 200 205 Arg Val Leu Asp Val Ile Leu Glu Val Phe Glu CysArg Pro Glu His 210 215 220 Asp Asp Phe Phe Ile Ser Leu Leu Glu Ser TyrMet Ser Met Cys Glu 225 230 235 240 Pro Gln Thr Leu Cys His Ile Leu GlyPhe Lys Phe Lys Phe Tyr Gln 245 250 255 Glu Pro Asn Gly Glu Thr Pro SerSer Leu Tyr Arg Val Ala Ala Val 260 265 270 Leu Leu Gln Phe Asn Leu IleAsp Leu Asp Asp Leu Tyr Val His Leu 275 280 285 Leu Pro Ala Asp Asn CysIle Met Asp Glu His Lys Arg Glu Ile Ala 290 295 300 Glu Ala Lys Gln IleVal Arg Lys Leu Thr Met Val Val Leu Ser Ser 305 310 315 320 Glu Lys MetAsp Glu Arg Glu Lys Glu Lys Glu Lys Glu Glu Glu Lys 325 330 335 Val GluLys Pro Pro Asp Asn Gln Lys Leu Gly Leu Leu Glu Ala Leu 340 345 350 LeuLys Ile Gly Asp Trp Gln His Ala Gln Asn Ile Met Asp Gln Met 355 360 365Pro Pro Tyr Tyr Ala Ala Ser His Lys Leu Ile Ala Leu Ala Ile Cys 370 375380 Lys Leu Ile His Ile Thr Ile Glu Pro Leu Tyr Arg Arg Val Gly Val 385390 395 400 Pro Lys Gly Ala Lys Gly Ser Pro Val Asn Ala Leu Gln Asn LysArg 405 410 415 Ala Pro Lys Gln Ala Glu Ser Phe Glu Asp Leu Arg Arg AspVal Phe 420 425 430 Asn Met Phe Cys Tyr Leu Gly Pro His Leu Ser His AspPro Ile Leu 435 440 445 Phe Ala Lys Val Val Arg Ile Gly Lys Ser Phe MetLys Glu Phe Gln 450 455 460 Ser Asp Gly Ser Lys Gln Glu Asp Lys Glu LysThr Glu Val Ile Leu 465 470 475 480 Ser Cys Leu Leu Ser Ile Thr Asp GlnVal Leu Leu Pro Ser Leu Ser 485 490 495 Leu Met Asp Cys Asn Ala Cys MetSer Glu Glu Leu Trp Gly Met Phe 500 505 510 Lys Thr Phe Pro Tyr Gln HisArg Tyr Arg Leu Tyr Gly Gln Trp Lys 515 520 525 Asn Glu Thr Tyr Asn SerHis Pro Leu Leu Val Lys Val Lys Ala Gln 530 535 540 Thr Ile Asp Arg AlaLys Tyr Ile Met Lys Arg Leu Thr Lys Glu Asn 545 550 555 560 Val Lys ProSer Gly Arg Gln Ile Gly Lys Leu Ser His Ser Asn Pro 565 570 575 Thr IleLeu Phe Asp Tyr Ile Leu Ser Gln Ile Gln Lys Tyr Asp Asn 580 585 590 LeuIle Thr Pro Val Val Asp Ser Leu Lys Tyr Leu Thr Ser Leu Asn 595 600 605Tyr Asp Val Leu Ala Tyr Cys Ile Ile Glu Ala Leu Ala Asn Pro Glu 610 615620 Lys Glu Arg Met Lys His Asp Asp Thr Thr Ile Ser Ser Trp Leu Gln 625630 635 640 Ser Leu Ala Ser Phe Cys Gly Ala Val Phe Arg Lys Tyr Pro IleAsp 645 650 655 Leu Ala Gly Leu Leu Gln Tyr Val Ala Asn Gln Leu Lys AlaGly Lys 660 665 670 Ser Phe Asp Leu Leu Ile Leu Lys Glu Val Val Gln LysMet Ala Gly 675 680 685 Ile Glu Ile Thr Glu Glu Met Thr Met Glu Gln LeuGlu Ala Met Thr 690 695 700 Gly Gly Glu Gln Leu Lys Ala Glu Gly Gly TyrPhe Gly Gln Ile Arg 705 710 715 720 Asn Thr Lys Lys Ser Ser Gln Arg LeuLys Asp Ala Leu Leu Asp His 725 730 735 Asp Leu Ala Leu Pro Leu Cys LeuLeu Met Ala Gln Gln Arg Asn Gly 740 745 750 Val Ile Phe Gln Glu Gly GlyGlu Lys His Leu Lys Leu Val Gly Lys 755 760 765 Leu Tyr Asp Gln Cys HisAsp Thr Leu Val Gln Phe Gly Gly Phe Leu 770 775 780 Ala Ser Asn Leu SerThr Glu Asp Tyr Ile Lys Arg Val Pro Ser Ile 785 790 795 800 Asp Val LeuCys Asn Glu Phe His Thr Pro His Asp Ala Ala Phe Phe 805 810 815 Leu SerArg Pro Met Tyr Ala His His Ile Ser Ser Lys Tyr Asp Glu 820 825 830 LeuLys Lys Ser Glu Lys Gly Ser Lys Gln Gln His Lys Val His Lys 835 840 845Tyr Ile Thr Ser Cys Glu Met Val Met Ala Pro Val His Glu Ala Val 850 855860 Val Ser Leu His Val Ser Lys Val Trp Asp Asp Ile Ser Pro Gln Phe 865870 875 880 Tyr Ala Thr Phe Trp Ser Leu Thr Met Tyr Asp Leu Ala Val ProHis 885 890 895 Thr Ser Tyr Glu Arg Glu Val Asn Lys Leu Lys Val Gln MetLys Ala 900 905 910 Ile Asp Asp Asn Gln Glu Met Pro Pro Asn Lys Lys LysLys Glu Lys 915 920 925 Glu Arg Cys Thr Ala Leu Gln Asp Lys Leu Leu GluGlu Glu Lys Lys 930 935 940 Gln Met Glu His Val Gln Arg Val Leu Gln ArgLeu Lys Leu Glu Lys 945 950 955 960 Asp Asn Trp Leu Leu Ala Lys Ser ThrLys Asn Glu Thr Ile Thr Lys 965 970 975 Phe Leu Gln Leu Cys Ile Phe ProArg Cys Ile Phe Ser Ala Ile Asp 980 985 990 Ala Val Tyr Cys Ala Arg PheVal Glu Leu Val His Gln Gln Lys Thr 995 1000 1005 Pro Asn Phe Ser ThrLeu Leu Cys Tyr Asp Arg Val Phe Ser Asp 1010 1015 1020 Ile Ile Tyr ThrVal Ala Ser Cys Thr Glu Asn Glu Ala Ser Arg 1025 1030 1035 Tyr Gly ArgPhe Leu Cys Cys Met Leu Glu Thr Val Thr Arg Trp 1040 1045 1050 His SerAsp Arg Ala Thr Tyr Glu Lys Glu Cys Gly Asn Tyr Pro 1055 1060 1065 GlyPhe Leu Thr Ile Leu Arg Ala Thr Gly Phe Asp Gly Gly Asn 1070 1075 1080Lys Ala Asp Gln Leu Asp Tyr Glu Asn Phe Arg His Val Val His 1085 10901095 Lys Trp His Tyr Lys Leu Thr Lys Ala Ser Val His Cys Leu Glu 11001105 1110 Thr Gly Glu Tyr Thr His Ile Arg Asn Ile Leu Ile Val Leu Thr1115 1120 1125 Lys Ile Leu Pro Trp Tyr Pro Lys Val Leu Asn Leu Gly GlnAla 1130 1135 1140 Leu Glu Arg Arg Val His Lys Ile Cys Gln Glu Glu LysGlu Lys 1145 1150 1155 Arg Pro Asp Leu Tyr Ala Leu Ala Met Gly Tyr SerGly Gln Leu 1160 1165 1170 Lys Ser Arg Lys Ser Tyr Met Ile Pro Glu AsnGlu Phe His His 1175 1180 1185 Lys Asp Pro Pro Pro Arg Asn Ala Val AlaSer Val Gln Asn Gly 1190 1195 1200 Pro Gly Gly Gly Pro Ser Ser Ser SerIle Gly Ser Ala Ser Lys 1205 1210 1215 Ser Asp Glu Ser Ser Thr Glu GluThr Asp Lys Ser Arg Glu Arg 1220 1225 1230 Ser Gln Cys Gly Val Lys AlaVal Asn Lys Ala Ser Ser Thr Thr 1235 1240 1245 Pro Lys Gly Asn Ser SerAsn Gly Asn Ser Gly Ser Asn Ser Asn 1250 1255 1260 Lys Ala Val Lys GluAsn Asp Lys Glu Lys Gly Lys Glu Lys Glu 1265 1270 1275 Lys Glu Lys LysGlu Lys Thr Pro Ala Thr Thr Pro Glu Ala Arg 1280 1285 1290 Val Leu GlyLys Asp Gly Lys Glu Lys Pro Lys Glu Glu Arg Pro 1295 1300 1305 Asn LysAsp Glu Lys Ala Arg Glu Thr Lys Glu Arg Thr Pro Lys 1310 1315 1320 SerAsp Lys Glu Lys Glu Lys Phe Lys Lys Glu Glu Lys Ala Lys 1325 1330 1335Asp Glu Lys Phe Lys Thr Thr Val Pro Asn Ala Glu Ser Lys Ser 1340 13451350 Thr Gln Glu Arg Glu Arg Glu Lys Glu Pro Ser Arg Glu Arg Asp 13551360 1365 Ile Ala Lys Glu Met Lys Ser Lys Glu Asn Val Lys Gly Gly Glu1370 1375 1380 Lys Thr Pro Val Ser Gly Ser Leu Lys Ser Pro Val Pro ArgSer 1385 1390 1395 Asp Ile Pro Glu Pro Glu Arg Glu Gln Lys Arg Arg LysIle Asp 1400 1405 1410 Thr His Pro Ser Pro Ser His Ser Ser Thr Val LysAsp Ser Leu 1415 1420 1425 Ile Glu Leu Lys Glu Ser Ser Ala Lys Leu TyrIle Asn His Thr 1430 1435 1440 Pro Pro Pro Leu Ser Lys Ser Lys Glu ArgGlu Met Asp Lys Lys 1445 1450 1455 Asp Leu Asp Lys Ser Arg Glu Arg SerArg Glu Arg Glu Lys Lys 1460 1465 1470 Asp Glu Lys Asp Arg Lys Glu ArgLys Arg Asp His Ser Asn Asn 1475 1480 1485 Asp Arg Glu Val Pro Pro AspLeu Thr Lys Arg Arg Lys Glu Glu 1490 1495 1500 Asn Gly Thr Met Gly ValSer Lys His Lys Ser Glu Ser Pro Cys 1505 1510 1515 Glu Ser Pro Tyr ProAsn Glu Lys Asp Lys Glu Lys Asn Lys Ser 1520 1525 1530 Lys Ser Ser GlyLys Glu Lys Gly Ser Asp Ser Phe Lys Ser Glu 1535 1540 1545 Lys Met AspLys Ile Ser Ser Gly Gly Lys Lys Glu Ser Arg His 1550 1555 1560 Asp LysGlu Lys Ile Glu Lys Lys Glu Lys Arg Asp Ser Ser Gly 1565 1570 1575 GlyLys Glu Glu Lys Lys His His Lys Ser Ser Asp Lys His Arg 1580 1585 159020 2561 DNA Homo sapiens CDS (918)..(1253) 20 gttttctgtt cctgtgttagtttgctgaga atgatggctt ccagcttcat ccatgtccct 60 acaaaggaca tgaactcatccttttttatg ggtgcatagt attccatggt gtatatgtgc 120 cacattttct ttatccggtctatcattggt gagcatttgg gttggttcca agtctttggt 180 attgtaaata gtgctgcagtaaacatatgt gtgcatgtgt ctttatggta gaatgattta 240 taatgctttg ggtatatacccagtaatggg attgctgggt caaatggtat ttctggtact 300 ggatccttga ggaatcgccacactgtcttc cacaatggtt gaactaattt acactcccac 360 caacagtgta aaagtgttcctatttctcca cagcctggct aacatggcga ggccccgtct 420 ctgctaaaaa tgcaaaaattagctgggcgt ggtggcggat gcctgtagtc ccagctactc 480 gggcagctga tgaggcttgaacctgggagg tggaggttgc agtgagccga gatcgcacca 540 ttgcactcca gcctgggtgacaagtgtgaa actgtgtctc aaaaataaat aaataaataa 600 aaataaaaat ttgaacttaaaatttctgtg tacatttcta ttttcttatg agaaattgct 660 gaaaatggac ttattctaccaaaggggtac aagctttatg aaggctcttg atacgtactg 720 ccaaattgct ttctgggaaggttctttcat tttatgctcc cacaagcagt atgttagagt 780 gtccatttta ccctattctcactagcactg gattttatta tttatattct tattttgata 840 ggcataaaat atgctattattttactagta ttacaatgaa ttattggtga ctaggaaaaa 900 tattaaatat aggtttt atggta ttt att agt ttt tgc cct att tcc ttt 950 Met Val Phe Ile Ser Phe CysPro Ile Ser Phe 1 5 10 ttg ttt gtt ttt tgt ttt tgt ttt atg tgc agt cgactc ttg aac gat 998 Leu Phe Val Phe Cys Phe Cys Phe Met Cys Ser Arg LeuLeu Asn Asp 15 20 25 gca gtt ttg tac tgc atg ggc cca ctt aat aat gag ggtttt ttt ttt 1046 Ala Val Leu Tyr Cys Met Gly Pro Leu Asn Asn Glu Gly PhePhe Phe 30 35 40 cca ata aat aca gta tca gtg tgt tcc tca tct gca acc aaacgc gga 1094 Pro Ile Asn Thr Val Ser Val Cys Ser Ser Ser Ala Thr Lys ArgGly 45 50 55 tcc aaa ata cag tcg tcc cta agt atc ctt ggg gga ttg gtt tcaggg 1142 Ser Lys Ile Gln Ser Ser Leu Ser Ile Leu Gly Gly Leu Val Ser Gly60 65 70 75 att gcc ctt gag tac caa acc cca tgc att ctc aag tcc tgc agtggc 1190 Ile Ala Leu Glu Tyr Gln Thr Pro Cys Ile Leu Lys Ser Cys Ser Gly80 85 90 cct gtg gaa ccc atg gat atg aag tca gcc ctc tgt atc cgt ctc cag1238 Pro Val Glu Pro Met Asp Met Lys Ser Ala Leu Cys Ile Arg Leu Gln 95100 105 gag ttt cat att ttg tgaataccgt atttttgatc taggtttggt tgtggatgca1293 Glu Phe His Ile Leu 110 gaacctgttg atacggaggg ccaactgtat ttattgaaacaaatccatgt acaagtggac 1353 gcacgcagtt ctaacctgag ttgttcaagg ttcaaatgtacagtattcac aagatgcaaa 1413 acctgtgtac atgaggggca acttttctta tccgtgggttctgcagggct gctgaatgac 1473 ttgagtatgg gtggattttg gtgtctgcct gtaatgcttaccacaatcaa atgaacatat 1533 tcatcaccac acatagttac cattgtgtgt gcatgtgtgtgtgtggtgag gacacttaag 1593 attactcttt tagcaaattt caagtaactt ttgactattattttcttgac gaagtatttg 1653 tattttccta ttgatttcta agaacttttc atatagtcaggtacaacttt acatagattg 1713 ccattgtttt tttttcttta gtcttcttta tggtaattttaacatacaca aaatattttt 1773 taaattttta attttttgtt ggtatatagt aggtatatatatttatggtg tacatgagaa 1833 gttttgatac aggcatgcaa tgtgtaataa tcacatcattgatcaccaag gaaatgcaaa 1893 tcaaaaccac aaagtacttt tttaaagttt atggagtcaaatctattttt ccttgtcatc 1953 tgttttcttc cagtactttt atgcttagaa agtccttctgcatatagagg acaaataaac 2013 atttattctt tatagttatt ttatggattc actttgtttttacatttagt tctttaattc 2073 atctggaatt tactatgaca agtagtatga agacaaaaaaatcgatcctt attttgcacc 2133 aaatagccaa ttgtcacgta attgtttatg gaataatacttccttttacc tctgattttg 2193 taatgctgag tttattagac aacaaaatct tatatattctaagatctgtt tctgggctct 2253 ttccattcca ttgaactatg ccataccatt ttaaatattgtagttttaca tttttccttg 2313 gctattttga cctgtttatt cttcttgaac ttagtaggcccaccgattaa gattttattt 2373 ggaaaagcag tgtctctgct tttaatgagc tgagtgaggcaaatcactta acctctccat 2433 gcctttgttt cttcatctgt aaagtgggga aaagagtatctccttttgcc caagttccag 2493 ggaaattgtg aggatcaaat gagatggtta tgaaaacattttgaaaaagt aaaaaaaaaa 2553 aaaaaaaa 2561 21 112 PRT Homo sapiens 21 MetVal Phe Ile Ser Phe Cys Pro Ile Ser Phe Leu Phe Val Phe Cys 1 5 10 15Phe Cys Phe Met Cys Ser Arg Leu Leu Asn Asp Ala Val Leu Tyr Cys 20 25 30Met Gly Pro Leu Asn Asn Glu Gly Phe Phe Phe Pro Ile Asn Thr Val 35 40 45Ser Val Cys Ser Ser Ser Ala Thr Lys Arg Gly Ser Lys Ile Gln Ser 50 55 60Ser Leu Ser Ile Leu Gly Gly Leu Val Ser Gly Ile Ala Leu Glu Tyr 65 70 7580 Gln Thr Pro Cys Ile Leu Lys Ser Cys Ser Gly Pro Val Glu Pro Met 85 9095 Asp Met Lys Ser Ala Leu Cys Ile Arg Leu Gln Glu Phe His Ile Leu 100105 110 22 3856 DNA Homo sapiens CDS (578)..(844) 22 atggaatatgttttagccac cagctacctg tacttaaaaa caaaacccca aaaacctgct 60 catttgattttcagtaagag tctattaaaa attcttaaat cagaaaccag gtagtaaaca 120 atttctgtaaaagccgattt tcaagtggag acattttgac ctggagctag tgaattcaat 180 gaaaaaaacaaaaaacaaaa aacaaaaaaa gctaagagag acacattata tccaatgtat 240 gttataatacttatttaaag ggtatcataa tattttgagt ttggggaaag ttcaatccta 300 atgttaatgtttatgaggaa atgtgtaata ttcatgcatt tctatgcaat tctctacttg 360 ccacaagccaaagaagaaac aatcaattta caaataacac agaggcagta aatttgttgg 420 tggtgatgctagctaggcct attgtaattc cataattctg tagttttttt tcaacctgca 480 agtggtgaattgctaatgtt gctgggagcc aaagatatgg tgatatgtga aagtgtccag 540 gcagcgcttacattatgtaa ggcttggagg tattttg atg tca gta aaa tac ttt 595 Met Ser ValLys Tyr Phe 1 5 atg gga gta ata gga aaa tgt gta ctg ttg aaa tca tat ccagaa aat 643 Met Gly Val Ile Gly Lys Cys Val Leu Leu Lys Ser Tyr Pro GluAsn 10 15 20 tca gag ttt atg ttg aat ttt att tcc caa ctc aca ttt gag gtttac 691 Ser Glu Phe Met Leu Asn Phe Ile Ser Gln Leu Thr Phe Glu Val Tyr25 30 35 aag ttt tgc tta gtg tgc ttg gtg cta ctc gat caa ttg aga cac agt739 Lys Phe Cys Leu Val Cys Leu Val Leu Leu Asp Gln Leu Arg His Ser 4045 50 tcc tct ctg gtg ggg gtt cat gtc tgt gtc cag aca tct tgt tgg ctg787 Ser Ser Leu Val Gly Val His Val Cys Val Gln Thr Ser Cys Trp Leu 5560 65 70 tgc tct aat cac agt gat cat ttt gag ctg ttg tta aga aaa aca tgg835 Cys Ser Asn His Ser Asp His Phe Glu Leu Leu Leu Arg Lys Thr Trp 7580 85 ctt cca aca tagatgcctt gttttctcca acaaatattt aagctatatt 884 LeuPro Thr gccacctcca ttttagttgt ttctctttag atctggctgt cataatttatctgttttgct 944 tcatccaaga tgattgctgt aaacaggcat agggtgctgt cttcccttctaggcagccca 1004 gtaattccat ctcagataat ttctagttac ctgttggata cttacgtgaaggtctgaata 1064 aattatgatc attacgaaca tgatacatga gtaatgaatt aaaagaaatatttaaaagtt 1124 ttatatttta agtctccagg gagtaaggca ttgagaaaat ggggtaaatatttcttgtcg 1184 aagagaaatc aaatatgggt gaatcattga ctactgggag tccttgggtttattctcaga 1244 tctttcactt tttggcagta ttctggaagc aagttagtga cttgactgaagctcagtttg 1304 cacatctgtg aagaggacag taatttctgg tctcataggg ctgttaagagcatggaatgg 1364 aatccaattc ggcttcatct atctttattt ttcatgtaat ctgtcaggcaccatgttagt 1424 ggaatgtctt gtaaataatg aatcgtatag cctctggtct caaggatctcataaacctac 1484 tggacagata ttatgtattt tggtttccta catgacatcc aagttcatgaatcttttgaa 1544 ttctttccat acaacccagg atgcaagctt ctggtaagac aaatggatatttattaagat 1604 cctgtaagaa acaaggcaga aaattaaagt cattaggagt atagaaataaaagatttctt 1664 gggctttcac ctctgtaaac ttgaggagtt tggctaagtc agtagttggaagcgtagtaa 1724 ggtcagaagt caccgtcaac ttccgttaaa tcccaaagct tacaattatttaacagagga 1784 tcacctacgc taacagaatg ttgggatttt gtttgtttgg ggttttggtaaataattata 1844 tacattcagg ggtcttagta ctgggtagct tatataagtc caaaaatatgattgttagcc 1904 ttgccttttg attaataaaa tgggggaaat atgttgttaa aaaaaaaaaaacgaaaaagg 1964 gcaagaaact atttgaaaac caggcattgg gttgaattgg aagtgaatacacttcaaaag 2024 gtctgaggag aaaatattag aaaccactga tttggataat gtctaatagctcttttaact 2084 cttagtcttt tacctaaata tccttgatat ttacagcata gtaaaatctggttttccaag 2144 gattctgatg aaagaaaaga aaaaaaatga aaacagatgg acaatctgagaagtaactag 2204 tgattgatgg taaatgtgaa caatgcttca gaaaggaaat gaaatgtctgcagcagatag 2264 aagtgtgtaa attttgcctt cactttagag ctagaatcac tatgagtggtagcatttcag 2324 aatcagaaga atggaaagct cagttgatta tcatcacaca taggagtaaaaggaaaggtt 2384 cacattttta ttgacagctc atatcgaaaa gacagctcct cttagagagaagtgaattct 2444 cctccttctt gttgtttctt ctgccacctt tgccctcata cagcacgctctatcttcatc 2504 ttcttccctt ttccctcctc ctttcctgtc ttttcttatc ttcctccattctctccccat 2564 ttcctttctg tgctccctct cctttctgca ctcacctcct tcacctttcatctgtaggtg 2624 acactaaacc aaggtttaag aagagccacc ttggctgggt gcaatggcttacgcctgtaa 2684 tcctagcatt ttgggaggct gaggcaagtg gaacacaagg ccaggagttcgagaccagcc 2744 cagccaatgt ggtgaaaccc tgtctctact aaaaattcaa aaattagctgggcgtggtgg 2804 cacgcgcctg taatcccagc tactcgggag gctgaggtag gagaattgcttgaaaccaga 2864 aggtggaggt tgcagtgagc caagatcgca ccactgcact ccagcctgggcagaagagtg 2924 aaactccgtc tcaaaaaaaa aaaaaaaaaa aagccacctc acagagttgatggcagtgtg 2984 agtgctgctt tttgtacatt acctcattca gttctggaca caggaggggtctccaaatca 3044 tgctgcgtgg gccagggagt ctgatggaag aagtcatact tgagttatggctgtctcagg 3104 gatgctgtga gttgactagc ttgctgggag gctggagtct ggctcacacattcagaacat 3164 ttgcaggtta ctgagacaac cagtaccaag gacttgttct ggagactaaccagatatgga 3224 aaacactgag gtaggcagaa atcagtttgt gatgggctat tgatggtaaactaaggagct 3284 aaatggaaag ctctggcaaa cccttgaatg agagagaaat gatctaacagagaatcctct 3344 aacagaagta ggatgaacag attaaaggaa aaagtagggg gagaccaggtgggaatcttt 3404 cgcaccaagt caggaaggaa atagagttgt cacaaaagct gagggaaggaagaggaggag 3464 aggcaaattc aagggactaa agaggttgac tctttagaac ttggcgatgatgtgaaaatg 3524 agtaagaaag agtttaggag gccaggcgca gtggctcaca cctgtaatcccagcactttg 3584 ggaggccaag gagggcggat catctgaggt caggggttcg agaccagcgtgaccaacatg 3644 gtgaaacccc gtctctacta gaaagacaaa agattagctg ggcgtggtggcacacgcctg 3704 taatcccagc tacttgggag gctgagacag gagaattgcc tgggaggtggaggttgcagt 3764 gagccaagat agtgccattg cactccaacc tgggcaacaa gaacgaaactctgtttcaaa 3824 aaaaaaagaa aaacaaaaaa aaaaaaaaaa aa 3856 23 89 PRT Homosapiens 23 Met Ser Val Lys Tyr Phe Met Gly Val Ile Gly Lys Cys Val LeuLeu 1 5 10 15 Lys Ser Tyr Pro Glu Asn Ser Glu Phe Met Leu Asn Phe IleSer Gln 20 25 30 Leu Thr Phe Glu Val Tyr Lys Phe Cys Leu Val Cys Leu ValLeu Leu 35 40 45 Asp Gln Leu Arg His Ser Ser Ser Leu Val Gly Val His ValCys Val 50 55 60 Gln Thr Ser Cys Trp Leu Cys Ser Asn His Ser Asp His PheGlu Leu 65 70 75 80 Leu Leu Arg Lys Thr Trp Leu Pro Thr 85 24 3304 DNAHomo sapiens CDS (211)..(873) 24 agccagggac ctgcttggcc agcgacagatcctttgctgc tctgtctgcc ggttcttgag 60 gtgaatgtcg gaatccatta tctttcgggaaagctctctg gggcagggag cgtcctgggg 120 agttggaatt cagaaggaat ctctcagacgcaaatctcca tctcctccct gcctcacctg 180 ggcagccttt tcagactgtc tctgcccagaatg tca gga gag gcc aca gtc ttg 234 Met Ser Gly Glu Ala Thr Val Leu 1 5gcc tac cat gct cca gaa gaa cag gaa gga ctt cta gtt gtc aag gtt 282 AlaTyr His Ala Pro Glu Glu Gln Glu Gly Leu Leu Val Val Lys Val 10 15 20 gaagaa gaa aat tat gtt ttg gac cag gac ttt ggc ctt cag gaa aac 330 Glu GluGlu Asn Tyr Val Leu Asp Gln Asp Phe Gly Leu Gln Glu Asn 25 30 35 40 ccctgg agc caa gag gta ttc cgg cag aag ttc agg cag ttt agt tac 378 Pro TrpSer Gln Glu Val Phe Arg Gln Lys Phe Arg Gln Phe Ser Tyr 45 50 55 tct gactcc act ggc cct cgg gag gct ctg agc cgg ctg cga gag ctt 426 Ser Asp SerThr Gly Pro Arg Glu Ala Leu Ser Arg Leu Arg Glu Leu 60 65 70 tgc tgt cagtgg ttg agg ccg gag gtg cac tcc aag gag cag ata ctg 474 Cys Cys Gln TrpLeu Arg Pro Glu Val His Ser Lys Glu Gln Ile Leu 75 80 85 gag ctg ctg atgttg gag cag ttc ctg gcc atc ctt cct gag gag ctg 522 Glu Leu Leu Met LeuGlu Gln Phe Leu Ala Ile Leu Pro Glu Glu Leu 90 95 100 caa gct tgg ctgcga gag cat cgg cca gag aat gga gag gaa gct gtg 570 Gln Ala Trp Leu ArgGlu His Arg Pro Glu Asn Gly Glu Glu Ala Val 105 110 115 120 act atg ctggag gag ctg gaa aaa gaa ctg gag gag cca agg caa cag 618 Thr Met Leu GluGlu Leu Glu Lys Glu Leu Glu Glu Pro Arg Gln Gln 125 130 135 gac aca actcat ggc caa gaa atg ttc tgg cag gaa atg aca tcc aca 666 Asp Thr Thr HisGly Gln Glu Met Phe Trp Gln Glu Met Thr Ser Thr 140 145 150 gga gca ctgaag tct ctg tct ctg aat agc ccg gtg cag ccc tta gag 714 Gly Ala Leu LysSer Leu Ser Leu Asn Ser Pro Val Gln Pro Leu Glu 155 160 165 aac cag tgcaag act gag act cag gag tcc cag gct ttc cag gag aga 762 Asn Gln Cys LysThr Glu Thr Gln Glu Ser Gln Ala Phe Gln Glu Arg 170 175 180 gat ggg gtctca ctc tgt cac cca ggt tgg agt gca gtg gtg caa cca 810 Asp Gly Val SerLeu Cys His Pro Gly Trp Ser Ala Val Val Gln Pro 185 190 195 200 cgg ctcact gca gca gcc ttg aac ccc tgg gtt agg gtg atc ctc ctg 858 Arg Leu ThrAla Ala Ala Leu Asn Pro Trp Val Arg Val Ile Leu Leu 205 210 215 cct cggcct cca gag tagctgggac tgcggttgta caccaccatg cctggctaaa 913 Pro Arg ProPro Glu 220 tatccataat attcaaagct cagtattctg ttatttaatt ttggcttcattggcaagaca 973 gtccctaaga tggagatgaa tacattttca gtaatagaaa ccacataatcatttgaacag 1033 ggaaagttta atgttaagaa ttattaacta ctaagtgtta taacaaaaagtgaaactcaa 1093 aagaatacag caataacaga tatagagtgt ctctagggct gaggcagaacatcaaaggta 1153 agaacaaatt tgcaggaggg tgccacaact tcccctttcc tgccaggtcttagatccagg 1213 ccttgttgga gagggcacag ccacagccca ctggatggag atgccactgcagtgctgagc 1273 tggcagaact cactgaggag ccacactctg gggtgctaga agctccccatggggagctga 1333 cctggtacag aacttgctgg gaagctaccc atggggatgg ggcctttggaactcattggg 1393 atgtgcactg ctgggtgtcc catgtgctac agaaacaaac acaaagaacatgccagaacc 1453 aggaagaaaa gccctttctt ccagttcctc tgcaaccccc tctattgataaagctcacag 1513 catgccagct ggcaaatagt ccagtatcac agacagggca atgaagcgtagatttgaaac 1573 tgaggcaata aattgatagc tgtcacagat gccagggatt agaactgaaaggactttgat 1633 tatgttattg gcaaaatcat ccttatgggc agcagatata tcaggtataccagcttgttc 1693 tcattaatct tttgttaaat ctgactaccc ttctgatttt gtcttcaccaagcaatctta 1753 ttaacttcct atgaagctta gctgtaataa gaaaattgca tttgttcagtctggtccatg 1813 tgatggttac attactcatt aattctcatt ctgtttttat tactgagtttcacgggctta 1873 gttattaaga gtctacccca agagataaat ctattttttg tatgatgataaaattaggta 1933 tatgaggacc taagcccaaa ggccagaccc tggacttcgg cagttcaccaaaggaatcca 1993 taccatccat ccactgaatt cttctgggaa actgcttccc aaccttccccaggcatcata 2053 ccctgatact accattagcc aagcaggccc tcttaagtat cttctgcaccaagcaggtgc 2113 tacattaaaa cgggttttga aaattcatct caaggaaatc aagctgtctctatttgcaga 2173 taatatgatc ccatgtctag aaaaccctat cgtctcagcc ccaaagcttcttaagccaag 2233 aagcaactac agcaaagtct caggatacaa aattaatgtg caaaaatcataagcattcct 2293 atatacagag attcctatat ctctgtgtct gtactgcaca cctgaacaacaatagacaac 2353 cagagagcca aacatgatta actcccattc acaattgcta caaagagaataaaataccta 2413 ggaatacagc taacaaggga ggtgaagggc ctcttcaagg agaactacaaaccactgctc 2473 aaggaaatca gagaggacac aaacaaatgg agaaacattc catgcttatggataggaaga 2533 attaatatca tgaaaatggc catactgccc aaagtaattt atagattcagtgttattccc 2593 attaaactac cattgacatt cttcacagaa ttagaaaaaa atactttaaaattcatatgg 2653 tacaaaaaaa agagccctta tagccaagac aatcctaagc aaaaagaacaaagctggagg 2713 catcatgcca cctgccttca atctgtacta caaggctact ataacccaaacagcatggta 2773 ctggtacaaa aacagacaca tagaccaatg gaacagaata gagatctgagaaataagact 2833 gcacatctac aaccacttga tatttgacaa acctgacaca aacaagcaatggggaaagga 2893 ttacctattt gataaatggt gctgggaaaa ctggctagcc atatgcagaaaactgaaact 2953 ggatccctcc tttacacctt gtacaaaaat aaactcaaca tggactaaagacttaaatgt 3013 aaaacccaaa actataaaat ccctagtaaa aaaatctagg taataccattcaggacatag 3073 gcatgggcaa agatttcatg atgaaaatgt caaaagcaat tgcaatagaagcaaaaattg 3133 acaaatggga cgtaattaaa gagcttttgc acagcaaaag aacctattataagagtgaac 3193 agacaacgta cagaatggga gaaaattttt gcaatctatc catctgacaaaggtctaata 3253 tccaggatct acaagaaact taaacaaatt tacaaaaaaa aaaacaaaaa a3304 25 221 PRT Homo sapiens 25 Met Ser Gly Glu Ala Thr Val Leu Ala TyrHis Ala Pro Glu Glu Gln 1 5 10 15 Glu Gly Leu Leu Val Val Lys Val GluGlu Glu Asn Tyr Val Leu Asp 20 25 30 Gln Asp Phe Gly Leu Gln Glu Asn ProTrp Ser Gln Glu Val Phe Arg 35 40 45 Gln Lys Phe Arg Gln Phe Ser Tyr SerAsp Ser Thr Gly Pro Arg Glu 50 55 60 Ala Leu Ser Arg Leu Arg Glu Leu CysCys Gln Trp Leu Arg Pro Glu 65 70 75 80 Val His Ser Lys Glu Gln Ile LeuGlu Leu Leu Met Leu Glu Gln Phe 85 90 95 Leu Ala Ile Leu Pro Glu Glu LeuGln Ala Trp Leu Arg Glu His Arg 100 105 110 Pro Glu Asn Gly Glu Glu AlaVal Thr Met Leu Glu Glu Leu Glu Lys 115 120 125 Glu Leu Glu Glu Pro ArgGln Gln Asp Thr Thr His Gly Gln Glu Met 130 135 140 Phe Trp Gln Glu MetThr Ser Thr Gly Ala Leu Lys Ser Leu Ser Leu 145 150 155 160 Asn Ser ProVal Gln Pro Leu Glu Asn Gln Cys Lys Thr Glu Thr Gln 165 170 175 Glu SerGln Ala Phe Gln Glu Arg Asp Gly Val Ser Leu Cys His Pro 180 185 190 GlyTrp Ser Ala Val Val Gln Pro Arg Leu Thr Ala Ala Ala Leu Asn 195 200 205Pro Trp Val Arg Val Ile Leu Leu Pro Arg Pro Pro Glu 210 215 220 26 2319DNA Homo sapiens CDS (280)..(1923) 26 cgctcccgga gctgggcgga gcggggcgcagcccacgtgg ttcgggcggg aggcgccggg 60 acgtggccag ttgcccgcct gccccggagagccaggcgct aaccagccgc tctgcgcccc 120 gcgccctgct tgcccccatt atccagccttgccccggcgc cctgacctga cgccctggcc 180 tgacgccctg cttcgtcgcc tcctttctctcccaggtgct ggaccaggga ctgagcgtcc 240 cccggagagg gtccggtgtg accccgacaagaagcagaa atg ggg aag aaa ctg 294 Met Gly Lys Lys Leu 1 5 gat ctt tccaag ctc act gat gaa gag gcc cag cat gtc ttg gaa gtt 342 Asp Leu Ser LysLeu Thr Asp Glu Glu Ala Gln His Val Leu Glu Val 10 15 20 gtt caa cga gatttt gac ctc cga agg aaa gaa gag gaa cgg cta gag 390 Val Gln Arg Asp PheAsp Leu Arg Arg Lys Glu Glu Glu Arg Leu Glu 25 30 35 gcg ttg aag ggc aagatt aag aag gaa agc tcc aag agg gag ctg ctt 438 Ala Leu Lys Gly Lys IleLys Lys Glu Ser Ser Lys Arg Glu Leu Leu 40 45 50 tcc gac act gcc cat ctgaac gag acc cac tgc gcc cgc tgc ctg cag 486 Ser Asp Thr Ala His Leu AsnGlu Thr His Cys Ala Arg Cys Leu Gln 55 60 65 ccc tac cag ctg ctt gtg aatagc aaa agg cag tgc ctg gaa tgt ggc 534 Pro Tyr Gln Leu Leu Val Asn SerLys Arg Gln Cys Leu Glu Cys Gly 70 75 80 85 ctc ttc acc tgc aaa agc tgtggc cgc gtc cac ccg gag gag cag ggc 582 Leu Phe Thr Cys Lys Ser Cys GlyArg Val His Pro Glu Glu Gln Gly 90 95 100 tgg atc tgt gac ccc tgc catctg gcc aga gtc gtg aag atc ggc tca 630 Trp Ile Cys Asp Pro Cys His LeuAla Arg Val Val Lys Ile Gly Ser 105 110 115 ctg gag tgg tac tat gag catgtg aaa gcc cgc ttc aag agg ttc gga 678 Leu Glu Trp Tyr Tyr Glu His ValLys Ala Arg Phe Lys Arg Phe Gly 120 125 130 agt gcc aag gtc atc cgg tccctc cac ggg cgg ctg cag ggt gga gct 726 Ser Ala Lys Val Ile Arg Ser LeuHis Gly Arg Leu Gln Gly Gly Ala 135 140 145 ggg cct gaa ctg ata tct gaagag aga agt gga gac agc gac cag aca 774 Gly Pro Glu Leu Ile Ser Glu GluArg Ser Gly Asp Ser Asp Gln Thr 150 155 160 165 gat gag gat gga gaa cctggc tca gag gcc cag gcc cag gcc cag ccc 822 Asp Glu Asp Gly Glu Pro GlySer Glu Ala Gln Ala Gln Ala Gln Pro 170 175 180 ttt ggc agc aaa aaa aagcgc ctc ctc tcc gtc cac gac ttc gac ttc 870 Phe Gly Ser Lys Lys Lys ArgLeu Leu Ser Val His Asp Phe Asp Phe 185 190 195 gag gga gac tca gat gactcc act cag cct caa ggt cac tcc ctg cac 918 Glu Gly Asp Ser Asp Asp SerThr Gln Pro Gln Gly His Ser Leu His 200 205 210 ctg tcc tca gtc cct gaggcc agg gac agc cca cag tcc ctc aca gat 966 Leu Ser Ser Val Pro Glu AlaArg Asp Ser Pro Gln Ser Leu Thr Asp 215 220 225 gag tcc tgc tca gag aaggca gcc cct cac aag gct gag ggc ctg gag 1014 Glu Ser Cys Ser Glu Lys AlaAla Pro His Lys Ala Glu Gly Leu Glu 230 235 240 245 gag gct gat act ggggcc tct ggg tgc cac tcc cat ccg gaa gag cag 1062 Glu Ala Asp Thr Gly AlaSer Gly Cys His Ser His Pro Glu Glu Gln 250 255 260 ccg acc agc atc tcacct tcc aga cac ggc gcc ctg gct gag ctc tgc 1110 Pro Thr Ser Ile Ser ProSer Arg His Gly Ala Leu Ala Glu Leu Cys 265 270 275 ccg cct gga ggc tcccac agg atg gcc ctg ggg act gct gct gca ctc 1158 Pro Pro Gly Gly Ser HisArg Met Ala Leu Gly Thr Ala Ala Ala Leu 280 285 290 ggg tcg aat gtc atcagg aat gag cag ctg ccc ctg cag tac ttg gcc 1206 Gly Ser Asn Val Ile ArgAsn Glu Gln Leu Pro Leu Gln Tyr Leu Ala 295 300 305 gat gtg gac acc tctgat gag gaa agc atc cgg gct cac gtg atg gcc 1254 Asp Val Asp Thr Ser AspGlu Glu Ser Ile Arg Ala His Val Met Ala 310 315 320 325 tcc cac cat tccaag cgg aga ggc cgg gcg tct tct gag agt cag atc 1302 Ser His His Ser LysArg Arg Gly Arg Ala Ser Ser Glu Ser Gln Ile 330 335 340 ttt gag ctg aataag cat att tca gct gtg gaa tgc ctg ctg acc tac 1350 Phe Glu Leu Asn LysHis Ile Ser Ala Val Glu Cys Leu Leu Thr Tyr 345 350 355 ctg gag aac acagtt gtg cct ccc ttg gcc aag ggt cta ggt gct gga 1398 Leu Glu Asn Thr ValVal Pro Pro Leu Ala Lys Gly Leu Gly Ala Gly 360 365 370 gtg cgc acg gaggcc gat gta gag gag gag gcc ctg agg agg aag ctg 1446 Val Arg Thr Glu AlaAsp Val Glu Glu Glu Ala Leu Arg Arg Lys Leu 375 380 385 gag gag ctg accagc aac gtc agt gac cag gag acc tcg tcc gag gag 1494 Glu Glu Leu Thr SerAsn Val Ser Asp Gln Glu Thr Ser Ser Glu Glu 390 395 400 405 gag gaa gccaag gac gaa aag gca gag ccc aac agg gac aaa tca gtt 1542 Glu Glu Ala LysAsp Glu Lys Ala Glu Pro Asn Arg Asp Lys Ser Val 410 415 420 ggg cct ctcccc cag gcg gac ccg gag gtt tca gac att gaa tcc agg 1590 Gly Pro Leu ProGln Ala Asp Pro Glu Val Ser Asp Ile Glu Ser Arg 425 430 435 att gca gccctg agg gcc gca ggg ctc acg gtg aag ccc tcg gga aag 1638 Ile Ala Ala LeuArg Ala Ala Gly Leu Thr Val Lys Pro Ser Gly Lys 440 445 450 ccc cgg aggaag tca aac ctc ccg ata ttt ctc cct cga gtg gct ggg 1686 Pro Arg Arg LysSer Asn Leu Pro Ile Phe Leu Pro Arg Val Ala Gly 455 460 465 aaa ctt ggcaag aga cca gag gac cca aat gca gac cct tca agt gag 1734 Lys Leu Gly LysArg Pro Glu Asp Pro Asn Ala Asp Pro Ser Ser Glu 470 475 480 485 gcc aaggca atg gct gtg ccc tat ctt ctg aga aga aag ttc agt aat 1782 Ala Lys AlaMet Ala Val Pro Tyr Leu Leu Arg Arg Lys Phe Ser Asn 490 495 500 tcc ctgaaa agt caa ggt aaa gat gat gat tct ttt gat cgg aaa tca 1830 Ser Leu LysSer Gln Gly Lys Asp Asp Asp Ser Phe Asp Arg Lys Ser 505 510 515 gtg taccga ggc tcg ctg aca cag aga aac ccc aac gcg agg aaa gga 1878 Val Tyr ArgGly Ser Leu Thr Gln Arg Asn Pro Asn Ala Arg Lys Gly 520 525 530 atg gccagc cac acc ttc gcg aaa cct gtg gtg gcc cac cag tcc 1923 Met Ala Ser HisThr Phe Ala Lys Pro Val Val Ala His Gln Ser 535 540 545 taacgggacaggacagagag acagagcagc cctgcactgt tttccctcca ccacagccat 1983 cctgtccctcattggctctg tgctttccac tatacacagt caccgtccca atgagaaaca 2043 agaaggagcaccctccacat ggactcccac ctgcaagtgg acagcgacat tcagtcctgc 2103 actgctcacctgggtttact gatgactcct ggctgcccca ccatcctctc tgatctgtga 2163 gaaacagctaagctgctgtg acttcccttt aggacaatgt tgtgtaaatc tttgaaggac 2223 acaccgaagacctttatact gtgatctttt acccctttca ctcttggctt tcttatgttg 2283 ctttcatgaatggaatggaa aaaagatgac tcagtt 2319 27 548 PRT Homo sapiens 27 Met Gly LysLys Leu Asp Leu Ser Lys Leu Thr Asp Glu Glu Ala Gln 1 5 10 15 His ValLeu Glu Val Val Gln Arg Asp Phe Asp Leu Arg Arg Lys Glu 20 25 30 Glu GluArg Leu Glu Ala Leu Lys Gly Lys Ile Lys Lys Glu Ser Ser 35 40 45 Lys ArgGlu Leu Leu Ser Asp Thr Ala His Leu Asn Glu Thr His Cys 50 55 60 Ala ArgCys Leu Gln Pro Tyr Gln Leu Leu Val Asn Ser Lys Arg Gln 65 70 75 80 CysLeu Glu Cys Gly Leu Phe Thr Cys Lys Ser Cys Gly Arg Val His 85 90 95 ProGlu Glu Gln Gly Trp Ile Cys Asp Pro Cys His Leu Ala Arg Val 100 105 110Val Lys Ile Gly Ser Leu Glu Trp Tyr Tyr Glu His Val Lys Ala Arg 115 120125 Phe Lys Arg Phe Gly Ser Ala Lys Val Ile Arg Ser Leu His Gly Arg 130135 140 Leu Gln Gly Gly Ala Gly Pro Glu Leu Ile Ser Glu Glu Arg Ser Gly145 150 155 160 Asp Ser Asp Gln Thr Asp Glu Asp Gly Glu Pro Gly Ser GluAla Gln 165 170 175 Ala Gln Ala Gln Pro Phe Gly Ser Lys Lys Lys Arg LeuLeu Ser Val 180 185 190 His Asp Phe Asp Phe Glu Gly Asp Ser Asp Asp SerThr Gln Pro Gln 195 200 205 Gly His Ser Leu His Leu Ser Ser Val Pro GluAla Arg Asp Ser Pro 210 215 220 Gln Ser Leu Thr Asp Glu Ser Cys Ser GluLys Ala Ala Pro His Lys 225 230 235 240 Ala Glu Gly Leu Glu Glu Ala AspThr Gly Ala Ser Gly Cys His Ser 245 250 255 His Pro Glu Glu Gln Pro ThrSer Ile Ser Pro Ser Arg His Gly Ala 260 265 270 Leu Ala Glu Leu Cys ProPro Gly Gly Ser His Arg Met Ala Leu Gly 275 280 285 Thr Ala Ala Ala LeuGly Ser Asn Val Ile Arg Asn Glu Gln Leu Pro 290 295 300 Leu Gln Tyr LeuAla Asp Val Asp Thr Ser Asp Glu Glu Ser Ile Arg 305 310 315 320 Ala HisVal Met Ala Ser His His Ser Lys Arg Arg Gly Arg Ala Ser 325 330 335 SerGlu Ser Gln Ile Phe Glu Leu Asn Lys His Ile Ser Ala Val Glu 340 345 350Cys Leu Leu Thr Tyr Leu Glu Asn Thr Val Val Pro Pro Leu Ala Lys 355 360365 Gly Leu Gly Ala Gly Val Arg Thr Glu Ala Asp Val Glu Glu Glu Ala 370375 380 Leu Arg Arg Lys Leu Glu Glu Leu Thr Ser Asn Val Ser Asp Gln Glu385 390 395 400 Thr Ser Ser Glu Glu Glu Glu Ala Lys Asp Glu Lys Ala GluPro Asn 405 410 415 Arg Asp Lys Ser Val Gly Pro Leu Pro Gln Ala Asp ProGlu Val Ser 420 425 430 Asp Ile Glu Ser Arg Ile Ala Ala Leu Arg Ala AlaGly Leu Thr Val 435 440 445 Lys Pro Ser Gly Lys Pro Arg Arg Lys Ser AsnLeu Pro Ile Phe Leu 450 455 460 Pro Arg Val Ala Gly Lys Leu Gly Lys ArgPro Glu Asp Pro Asn Ala 465 470 475 480 Asp Pro Ser Ser Glu Ala Lys AlaMet Ala Val Pro Tyr Leu Leu Arg 485 490 495 Arg Lys Phe Ser Asn Ser LeuLys Ser Gln Gly Lys Asp Asp Asp Ser 500 505 510 Phe Asp Arg Lys Ser ValTyr Arg Gly Ser Leu Thr Gln Arg Asn Pro 515 520 525 Asn Ala Arg Lys GlyMet Ala Ser His Thr Phe Ala Lys Pro Val Val 530 535 540 Ala His Gln Ser545 28 4779 DNA Homo sapiens CDS (121)..(3135) 28 catctccgca gtctgggccgctgggtgcag aggctgccgc agacccagcg gccatcgcct 60 ccctcaatcc caatatccattgtctcccac cccacctggc cctccacttc ccccacaacc 120 atg gcg cac gaa tcc gagagg agc tct cgt ctc ggg gtg ccc tgc ggg 168 Met Ala His Glu Ser Glu ArgSer Ser Arg Leu Gly Val Pro Cys Gly 1 5 10 15 gag ccg gca gag ctc ggaggt gat gct agc gag gag gat cac ccc caa 216 Glu Pro Ala Glu Leu Gly GlyAsp Ala Ser Glu Glu Asp His Pro Gln 20 25 30 gtc tgt gcc aag tgc tgc gcacaa ttc act gac cca act gaa ttc ctc 264 Val Cys Ala Lys Cys Cys Ala GlnPhe Thr Asp Pro Thr Glu Phe Leu 35 40 45 gcc cac cag aac gca tgt tct actgac cct cct gta atg gtg ata att 312 Ala His Gln Asn Ala Cys Ser Thr AspPro Pro Val Met Val Ile Ile 50 55 60 ggg ggc cag gag aac ccc aac aac tcttcg gcc tcc tct gaa ccc cgg 360 Gly Gly Gln Glu Asn Pro Asn Asn Ser SerAla Ser Ser Glu Pro Arg 65 70 75 80 cct gag ggt cac aat aat cct cag gtcatg gac aca gag cat agc aac 408 Pro Glu Gly His Asn Asn Pro Gln Val MetAsp Thr Glu His Ser Asn 85 90 95 ccc cca gat tct ggg tcc tcc gtg ccc acggat ccc acc tgg ggc cca 456 Pro Pro Asp Ser Gly Ser Ser Val Pro Thr AspPro Thr Trp Gly Pro 100 105 110 gag agg aga gga gag gag tct tca ggg catttc ctg gtc gct gcc aca 504 Glu Arg Arg Gly Glu Glu Ser Ser Gly His PheLeu Val Ala Ala Thr 115 120 125 ggt aca gcg gct ggg gga ggc ggg ggc ctgatc ttg gcc agt ccc aag 552 Gly Thr Ala Ala Gly Gly Gly Gly Gly Leu IleLeu Ala Ser Pro Lys 130 135 140 ctg gga gca acc cca tta cct cca gaa tcgacc cct gca ccc cct cct 600 Leu Gly Ala Thr Pro Leu Pro Pro Glu Ser ThrPro Ala Pro Pro Pro 145 150 155 160 cct cca cca ccc cct ccg ccc cca ggggta ggc agt ggc cac ttg aat 648 Pro Pro Pro Pro Pro Pro Pro Pro Gly ValGly Ser Gly His Leu Asn 165 170 175 atc ccc ctg atc ttg gaa gag cta cgggtg ctg cag cag cgg cag atc 696 Ile Pro Leu Ile Leu Glu Glu Leu Arg ValLeu Gln Gln Arg Gln Ile 180 185 190 cat cag atg cag atg act gag caa atctgc agg cag gtg ctg ttg ctt 744 His Gln Met Gln Met Thr Glu Gln Ile CysArg Gln Val Leu Leu Leu 195 200 205 ggc tcc tta ggc cag acg gtg ggt gcccct gcc agt ccc tca gag cta 792 Gly Ser Leu Gly Gln Thr Val Gly Ala ProAla Ser Pro Ser Glu Leu 210 215 220 cct ggg aca ggg act gcc tct tcc accaag ccc cta cta ccc ctc ttc 840 Pro Gly Thr Gly Thr Ala Ser Ser Thr LysPro Leu Leu Pro Leu Phe 225 230 235 240 agc ccc atc aag cct gtc caa accagc aag aca ctg gca tct tcc tcc 888 Ser Pro Ile Lys Pro Val Gln Thr SerLys Thr Leu Ala Ser Ser Ser 245 250 255 tcc tcc tcc tct tcc tct tca ggggca gaa acg ccc aag cag gcc ttc 936 Ser Ser Ser Ser Ser Ser Ser Gly AlaGlu Thr Pro Lys Gln Ala Phe 260 265 270 ttc cac ctt tac cac cca ctg gggtca cag cat cct ttc tct gct gga 984 Phe His Leu Tyr His Pro Leu Gly SerGln His Pro Phe Ser Ala Gly 275 280 285 ggg gtt ggg cga agc cac aaa cccacc cct gcc cct tcc cca gcc ttg 1032 Gly Val Gly Arg Ser His Lys Pro ThrPro Ala Pro Ser Pro Ala Leu 290 295 300 cca ggc agc aca gat cag ctg attgcc tcg cct cat ctg gca ttc cca 1080 Pro Gly Ser Thr Asp Gln Leu Ile AlaSer Pro His Leu Ala Phe Pro 305 310 315 320 agc acc acg gga cta ctg gcagca cag tgt ctt ggg gca gcc cga ggc 1128 Ser Thr Thr Gly Leu Leu Ala AlaGln Cys Leu Gly Ala Ala Arg Gly 325 330 335 ctt gag gcc act gcc tcc ccaggg ctc ctg aag cca aag aat gga agt 1176 Leu Glu Ala Thr Ala Ser Pro GlyLeu Leu Lys Pro Lys Asn Gly Ser 340 345 350 ggt gag ctg agc tac gga gaagtg atg ggt ccc ttg gag aag cct ggt 1224 Gly Glu Leu Ser Tyr Gly Glu ValMet Gly Pro Leu Glu Lys Pro Gly 355 360 365 gga agg cac aaa tgc cgc ttctgt gcc aaa gta ttt ggc agt gac agt 1272 Gly Arg His Lys Cys Arg Phe CysAla Lys Val Phe Gly Ser Asp Ser 370 375 380 gcc ctg cag atc cac ctt cgttcc cac acg ggt gag agg ccc tat aag 1320 Ala Leu Gln Ile His Leu Arg SerHis Thr Gly Glu Arg Pro Tyr Lys 385 390 395 400 tgc aat gtc tgt gga aaccgt ttt acc acc cgt ggc aac ctc aaa gtg 1368 Cys Asn Val Cys Gly Asn ArgPhe Thr Thr Arg Gly Asn Leu Lys Val 405 410 415 cat ttc cac cgg cat cgtgag aag tac cca cat gtg cag atg aac cca 1416 His Phe His Arg His Arg GluLys Tyr Pro His Val Gln Met Asn Pro 420 425 430 cac cca gta cca gag caccta gac tat gtc att acc agc agt ggc ttg 1464 His Pro Val Pro Glu His LeuAsp Tyr Val Ile Thr Ser Ser Gly Leu 435 440 445 cct tat ggt atg tcc gtgcca cca gag aag gcc gag gag gag gca gcc 1512 Pro Tyr Gly Met Ser Val ProPro Glu Lys Ala Glu Glu Glu Ala Ala 450 455 460 act cca ggt gga ggg gttgag cgc aag cct ctg gtg gcc tcc aca aca 1560 Thr Pro Gly Gly Gly Val GluArg Lys Pro Leu Val Ala Ser Thr Thr 465 470 475 480 gca ctc agt gcc acagag agc ctg act ctg ctc tcc acc agt gca ggc 1608 Ala Leu Ser Ala Thr GluSer Leu Thr Leu Leu Ser Thr Ser Ala Gly 485 490 495 aca gcc acg gct ccagga ctc cct gct ttc aat aag ttt gtg ctc atg 1656 Thr Ala Thr Ala Pro GlyLeu Pro Ala Phe Asn Lys Phe Val Leu Met 500 505 510 aaa gca gtg gaa cccaag aat aaa gct gat gaa aac acc ccc cca ggg 1704 Lys Ala Val Glu Pro LysAsn Lys Ala Asp Glu Asn Thr Pro Pro Gly 515 520 525 agt gag ggc tca gccatc agt gga gtg gca gaa agt agc acg gca act 1752 Ser Glu Gly Ser Ala IleSer Gly Val Ala Glu Ser Ser Thr Ala Thr 530 535 540 cgc atg caa cta agtaag ttg gtg act tca cta cca agc tgg gca ctg 1800 Arg Met Gln Leu Ser LysLeu Val Thr Ser Leu Pro Ser Trp Ala Leu 545 550 555 560 ctt acc aac cacttc aag tcc act ggc agc ttc ccc ttc ccc tat gtg 1848 Leu Thr Asn His PheLys Ser Thr Gly Ser Phe Pro Phe Pro Tyr Val 565 570 575 cta gag ccc ttgggg gcc tca ccc tct gag aca tca aag ctg cag caa 1896 Leu Glu Pro Leu GlyAla Ser Pro Ser Glu Thr Ser Lys Leu Gln Gln 580 585 590 ctg gta gaa aagatt gac cgg caa gga gct gtg gcg gtg acc tca gct 1944 Leu Val Glu Lys IleAsp Arg Gln Gly Ala Val Ala Val Thr Ser Ala 595 600 605 gcc tca gga gccccc acc acc tct gcc cct gca cct tca tcc tca gcc 1992 Ala Ser Gly Ala ProThr Thr Ser Ala Pro Ala Pro Ser Ser Ser Ala 610 615 620 tct tct gga cctaac cag tgt gtc atc tgt ctc cga gtg ctt agc tgt 2040 Ser Ser Gly Pro AsnGln Cys Val Ile Cys Leu Arg Val Leu Ser Cys 625 630 635 640 cct cgg gcccta cgc ctt cat tat ggc caa cat gga ggt gag agg ccc 2088 Pro Arg Ala LeuArg Leu His Tyr Gly Gln His Gly Gly Glu Arg Pro 645 650 655 ttc aaa tgcaaa gtg tgt ggc aga gcc ttc tcc acc agg ggt aat ctg 2136 Phe Lys Cys LysVal Cys Gly Arg Ala Phe Ser Thr Arg Gly Asn Leu 660 665 670 cgt gca catttc gtg ggc cac aag gcc agt cca gct gcc cgg gca cag 2184 Arg Ala His PheVal Gly His Lys Ala Ser Pro Ala Ala Arg Ala Gln 675 680 685 aat tcc tgcccc atc tgc cag aag aag ttc acc aat gct gtc act ctg 2232 Asn Ser Cys ProIle Cys Gln Lys Lys Phe Thr Asn Ala Val Thr Leu 690 695 700 cag cag catgtc cgg atg cac ctg ggg ggc cag atc ccc aac ggt ggt 2280 Gln Gln His ValArg Met His Leu Gly Gly Gln Ile Pro Asn Gly Gly 705 710 715 720 act gcactc cct gaa ggt gga gga gct gct cag gag aat ggc tcc gag 2328 Thr Ala LeuPro Glu Gly Gly Gly Ala Ala Gln Glu Asn Gly Ser Glu 725 730 735 caa tctaca gtc tcc ggg gca ggg agt ttc ccc cag cag cag tcc cag 2376 Gln Ser ThrVal Ser Gly Ala Gly Ser Phe Pro Gln Gln Gln Ser Gln 740 745 750 cag ccatca ccg gaa gag gag ttg tct gag gag gag gaa gag gag gat 2424 Gln Pro SerPro Glu Glu Glu Leu Ser Glu Glu Glu Glu Glu Glu Asp 755 760 765 gag gaagaa gag gaa gat gtg act gat gaa gat tcc ctg gca ggg aga 2472 Glu Glu GluGlu Glu Asp Val Thr Asp Glu Asp Ser Leu Ala Gly Arg 770 775 780 ggc tcagag agt gga ggt gag aag gca ata tca gtg aga ggt gat tca 2520 Gly Ser GluSer Gly Gly Glu Lys Ala Ile Ser Val Arg Gly Asp Ser 785 790 795 800 gaagag gca tct ggg gca gag gag gag gtg ggg aca gtg gcg gca gca 2568 Glu GluAla Ser Gly Ala Glu Glu Glu Val Gly Thr Val Ala Ala Ala 805 810 815 gccaca gct ggg aag gag atg gac agt aat gag aaa act act caa cag 2616 Ala ThrAla Gly Lys Glu Met Asp Ser Asn Glu Lys Thr Thr Gln Gln 820 825 830 tcttct ttg cca cca cca cca cca cct gac agc ctg gat cag cct cag 2664 Ser SerLeu Pro Pro Pro Pro Pro Pro Asp Ser Leu Asp Gln Pro Gln 835 840 845 ccaatg gag cag gga agc agt ggt gtt tta gga ggc aag gaa gag ggg 2712 Pro MetGlu Gln Gly Ser Ser Gly Val Leu Gly Gly Lys Glu Glu Gly 850 855 860 ggcaaa ccg gag aga agc tca agt ccg gca tca gca ctc acc cca gaa 2760 Gly LysPro Glu Arg Ser Ser Ser Pro Ala Ser Ala Leu Thr Pro Glu 865 870 875 880ggg gaa gcc acc agc gtg acc ttg gta gag gag ctg agc ctg cag gag 2808 GlyGlu Ala Thr Ser Val Thr Leu Val Glu Glu Leu Ser Leu Gln Glu 885 890 895gca atg aga aag gag cca gga gag agc agc agc aga aag gcc tgc gaa 2856 AlaMet Arg Lys Glu Pro Gly Glu Ser Ser Ser Arg Lys Ala Cys Glu 900 905 910gtg tgt ggc cag gcc ttt ccc tcc cag gca gct ctg gag gag cat cag 2904 ValCys Gly Gln Ala Phe Pro Ser Gln Ala Ala Leu Glu Glu His Gln 915 920 925aag acc cac ccc aag gag ggg ccg ctc ttc act tgt gtt ttc tgc agg 2952 LysThr His Pro Lys Glu Gly Pro Leu Phe Thr Cys Val Phe Cys Arg 930 935 940cag ggc ttt ctt gag cgg gct acc ctc aag aag cat atg ctc ctg gca 3000 GlnGly Phe Leu Glu Arg Ala Thr Leu Lys Lys His Met Leu Leu Ala 945 950 955960 cac cac cag gta cag ccc ttt gcc ccc cat ggc cct cag aat att gct 3048His His Gln Val Gln Pro Phe Ala Pro His Gly Pro Gln Asn Ile Ala 965 970975 gct ctt tct cta gtc cct ggc tgt tcg cct tcc atc acc tcc aca ggg 3096Ala Leu Ser Leu Val Pro Gly Cys Ser Pro Ser Ile Thr Ser Thr Gly 980 985990 ctc tcc ccc ttt ccc cga aaa gat gac ccc acg atc cca tgagcctgtt 3145Leu Ser Pro Phe Pro Arg Lys Asp Asp Pro Thr Ile Pro 995 1000 1005tttctgtacc tgctgctctt tgtcccacag agcagaaaca gcttcacaaa aggacctccc 3205agagttatga gccctgattt tgtctttttc tctaagttct taacatgtta tgtccctagt 3265ggcttttctg tagtccctga gcttggaaat tactgtgctt acaaggggat ggccccctaa 3325ggaatttttc ttccctcctc attctttgta cctgaggaac atagattctc tgcagctttc 3385tcaaggggaa ccctctccag cttccctggt gtgacccttc ttccccctcc tctctcctct 3445ccctttccct ttggtaggtg cacctgagca cctacatttg gcattgcagc ctagccaaaa 3505agggctggca gctgtctctg gagggcccag tgccactcct ctggggtgac ctttctgctc 3565agctggtggg tatgggtccc ctatctttct agaaccagta tgtggcattc ctgtcaaatg 3625gcctgcccat gaagccctgg aattccagct ccacctccac taccactcca agcctggccc 3685caccagtgct gtttggccta ggaactgtgg ctgggaaggt gcctccaaca atgggatcca 3745gggaagccaa ggagaagaca gcccccctcc tatttcagcc tcctgcaccc aaggcagtgc 3805ctgagaagcc catcatagac aagaagtagc aaactgtaca ttccttcttc ctccccctgc 3865tccagaaggt gccggtactg aagatgctcc agtaattggt gacccaaccc taggaagtag 3925ggagaaatga aggaagggca taggaaaatt ttcccagtaa atcccctgat ggtcacatta 3985aggtaaaggt tttggctggt cagtgtgcca agacctctcc agcttctcat tcatgatgac 4045ctctcaaagt tgggaaacaa gctgatttct tgccaagagg tctcccagga gatatttggg 4105aaatgtgaag ttcgtatctt taaggagcat ttttggtcag catggttgat gaactaatga 4165tgagagagtt aaggaatgtt gctagaacat agggcttgct ggtacctatg tgactaagaa 4225agggacatga tgtaagggaa aaggcctcaa attcttgtga atgtctggac attctcgtta 4285atattctttt gggctaatag tgacatagtg tgcagaggtg taccagggat catgggggat 4345ttcctagcac tagtatgctt ctagttttag ataactccct cctttattcc ctggcccctt 4405gtattttcct tatcttcctc tttcaagacc cctacccatt ttgcctatcc gtaggctggg 4465gcttgtgtct ttgtcattgt ctggttctta agagtcccag actttgggag accagctcca 4525ggtggcgtcc tccctgcctc tccgtcttgt aatgagttgt agtatttact cttaacatag 4585gatcatttgg aacaggagtt ctgaggagga gagagtgagg gttttgctat tgactgactt 4645gaacgatggc ttctcctcaa gctgtaggct ccagagcttc ctaacctagt aaaatgtcaa 4705gaacagacgg gagatattag tgtctttccc tctatcatta aaggtgtttt aaccaaaaaa 4765aaaaaaaaaa aaaa 4779 29 1005 PRT Homo sapiens 29 Met Ala His Glu Ser GluArg Ser Ser Arg Leu Gly Val Pro Cys Gly 1 5 10 15 Glu Pro Ala Glu LeuGly Gly Asp Ala Ser Glu Glu Asp His Pro Gln 20 25 30 Val Cys Ala Lys CysCys Ala Gln Phe Thr Asp Pro Thr Glu Phe Leu 35 40 45 Ala His Gln Asn AlaCys Ser Thr Asp Pro Pro Val Met Val Ile Ile 50 55 60 Gly Gly Gln Glu AsnPro Asn Asn Ser Ser Ala Ser Ser Glu Pro Arg 65 70 75 80 Pro Glu Gly HisAsn Asn Pro Gln Val Met Asp Thr Glu His Ser Asn 85 90 95 Pro Pro Asp SerGly Ser Ser Val Pro Thr Asp Pro Thr Trp Gly Pro 100 105 110 Glu Arg ArgGly Glu Glu Ser Ser Gly His Phe Leu Val Ala Ala Thr 115 120 125 Gly ThrAla Ala Gly Gly Gly Gly Gly Leu Ile Leu Ala Ser Pro Lys 130 135 140 LeuGly Ala Thr Pro Leu Pro Pro Glu Ser Thr Pro Ala Pro Pro Pro 145 150 155160 Pro Pro Pro Pro Pro Pro Pro Pro Gly Val Gly Ser Gly His Leu Asn 165170 175 Ile Pro Leu Ile Leu Glu Glu Leu Arg Val Leu Gln Gln Arg Gln Ile180 185 190 His Gln Met Gln Met Thr Glu Gln Ile Cys Arg Gln Val Leu LeuLeu 195 200 205 Gly Ser Leu Gly Gln Thr Val Gly Ala Pro Ala Ser Pro SerGlu Leu 210 215 220 Pro Gly Thr Gly Thr Ala Ser Ser Thr Lys Pro Leu LeuPro Leu Phe 225 230 235 240 Ser Pro Ile Lys Pro Val Gln Thr Ser Lys ThrLeu Ala Ser Ser Ser 245 250 255 Ser Ser Ser Ser Ser Ser Ser Gly Ala GluThr Pro Lys Gln Ala Phe 260 265 270 Phe His Leu Tyr His Pro Leu Gly SerGln His Pro Phe Ser Ala Gly 275 280 285 Gly Val Gly Arg Ser His Lys ProThr Pro Ala Pro Ser Pro Ala Leu 290 295 300 Pro Gly Ser Thr Asp Gln LeuIle Ala Ser Pro His Leu Ala Phe Pro 305 310 315 320 Ser Thr Thr Gly LeuLeu Ala Ala Gln Cys Leu Gly Ala Ala Arg Gly 325 330 335 Leu Glu Ala ThrAla Ser Pro Gly Leu Leu Lys Pro Lys Asn Gly Ser 340 345 350 Gly Glu LeuSer Tyr Gly Glu Val Met Gly Pro Leu Glu Lys Pro Gly 355 360 365 Gly ArgHis Lys Cys Arg Phe Cys Ala Lys Val Phe Gly Ser Asp Ser 370 375 380 AlaLeu Gln Ile His Leu Arg Ser His Thr Gly Glu Arg Pro Tyr Lys 385 390 395400 Cys Asn Val Cys Gly Asn Arg Phe Thr Thr Arg Gly Asn Leu Lys Val 405410 415 His Phe His Arg His Arg Glu Lys Tyr Pro His Val Gln Met Asn Pro420 425 430 His Pro Val Pro Glu His Leu Asp Tyr Val Ile Thr Ser Ser GlyLeu 435 440 445 Pro Tyr Gly Met Ser Val Pro Pro Glu Lys Ala Glu Glu GluAla Ala 450 455 460 Thr Pro Gly Gly Gly Val Glu Arg Lys Pro Leu Val AlaSer Thr Thr 465 470 475 480 Ala Leu Ser Ala Thr Glu Ser Leu Thr Leu LeuSer Thr Ser Ala Gly 485 490 495 Thr Ala Thr Ala Pro Gly Leu Pro Ala PheAsn Lys Phe Val Leu Met 500 505 510 Lys Ala Val Glu Pro Lys Asn Lys AlaAsp Glu Asn Thr Pro Pro Gly 515 520 525 Ser Glu Gly Ser Ala Ile Ser GlyVal Ala Glu Ser Ser Thr Ala Thr 530 535 540 Arg Met Gln Leu Ser Lys LeuVal Thr Ser Leu Pro Ser Trp Ala Leu 545 550 555 560 Leu Thr Asn His PheLys Ser Thr Gly Ser Phe Pro Phe Pro Tyr Val 565 570 575 Leu Glu Pro LeuGly Ala Ser Pro Ser Glu Thr Ser Lys Leu Gln Gln 580 585 590 Leu Val GluLys Ile Asp Arg Gln Gly Ala Val Ala Val Thr Ser Ala 595 600 605 Ala SerGly Ala Pro Thr Thr Ser Ala Pro Ala Pro Ser Ser Ser Ala 610 615 620 SerSer Gly Pro Asn Gln Cys Val Ile Cys Leu Arg Val Leu Ser Cys 625 630 635640 Pro Arg Ala Leu Arg Leu His Tyr Gly Gln His Gly Gly Glu Arg Pro 645650 655 Phe Lys Cys Lys Val Cys Gly Arg Ala Phe Ser Thr Arg Gly Asn Leu660 665 670 Arg Ala His Phe Val Gly His Lys Ala Ser Pro Ala Ala Arg AlaGln 675 680 685 Asn Ser Cys Pro Ile Cys Gln Lys Lys Phe Thr Asn Ala ValThr Leu 690 695 700 Gln Gln His Val Arg Met His Leu Gly Gly Gln Ile ProAsn Gly Gly 705 710 715 720 Thr Ala Leu Pro Glu Gly Gly Gly Ala Ala GlnGlu Asn Gly Ser Glu 725 730 735 Gln Ser Thr Val Ser Gly Ala Gly Ser PhePro Gln Gln Gln Ser Gln 740 745 750 Gln Pro Ser Pro Glu Glu Glu Leu SerGlu Glu Glu Glu Glu Glu Asp 755 760 765 Glu Glu Glu Glu Glu Asp Val ThrAsp Glu Asp Ser Leu Ala Gly Arg 770 775 780 Gly Ser Glu Ser Gly Gly GluLys Ala Ile Ser Val Arg Gly Asp Ser 785 790 795 800 Glu Glu Ala Ser GlyAla Glu Glu Glu Val Gly Thr Val Ala Ala Ala 805 810 815 Ala Thr Ala GlyLys Glu Met Asp Ser Asn Glu Lys Thr Thr Gln Gln 820 825 830 Ser Ser LeuPro Pro Pro Pro Pro Pro Asp Ser Leu Asp Gln Pro Gln 835 840 845 Pro MetGlu Gln Gly Ser Ser Gly Val Leu Gly Gly Lys Glu Glu Gly 850 855 860 GlyLys Pro Glu Arg Ser Ser Ser Pro Ala Ser Ala Leu Thr Pro Glu 865 870 875880 Gly Glu Ala Thr Ser Val Thr Leu Val Glu Glu Leu Ser Leu Gln Glu 885890 895 Ala Met Arg Lys Glu Pro Gly Glu Ser Ser Ser Arg Lys Ala Cys Glu900 905 910 Val Cys Gly Gln Ala Phe Pro Ser Gln Ala Ala Leu Glu Glu HisGln 915 920 925 Lys Thr His Pro Lys Glu Gly Pro Leu Phe Thr Cys Val PheCys Arg 930 935 940 Gln Gly Phe Leu Glu Arg Ala Thr Leu Lys Lys His MetLeu Leu Ala 945 950 955 960 His His Gln Val Gln Pro Phe Ala Pro His GlyPro Gln Asn Ile Ala 965 970 975 Ala Leu Ser Leu Val Pro Gly Cys Ser ProSer Ile Thr Ser Thr Gly 980 985 990 Leu Ser Pro Phe Pro Arg Lys Asp AspPro Thr Ile Pro 995 1000 1005 30 1687 DNA Homo sapiens CDS (121)..(717)30 catctccgca gtctgggccg ctgggtgcag aggctgccgc agacccagcg gccatcgcct 60ccctcaatcc caatatccat tgtctcccac cccacctggc cctccacttc ccccacaacc 120atg gcg cac gaa tcc gag agg agc tct cgt ctc ggg gtg ccc tgc ggg 168 MetAla His Glu Ser Glu Arg Ser Ser Arg Leu Gly Val Pro Cys Gly 1 5 10 15gag ccg gca gag ctc gga ggt gat gct agc gag gag gat cac ccc caa 216 GluPro Ala Glu Leu Gly Gly Asp Ala Ser Glu Glu Asp His Pro Gln 20 25 30 gtctgt gcc aag tgc tgc gca caa ttc act gac cca act gaa ttc ctc 264 Val CysAla Lys Cys Cys Ala Gln Phe Thr Asp Pro Thr Glu Phe Leu 35 40 45 gcc caccag aac gca tgt tct act gac cct cct gta atg gtg ata att 312 Ala His GlnAsn Ala Cys Ser Thr Asp Pro Pro Val Met Val Ile Ile 50 55 60 ggg ggc caggag aac ccc aac aac tct tcg gcc tcc tct gaa ccc cgg 360 Gly Gly Gln GluAsn Pro Asn Asn Ser Ser Ala Ser Ser Glu Pro Arg 65 70 75 80 cct gag ggtcac aat aat cct cag gtc atg gac aca gag cat agc aac 408 Pro Glu Gly HisAsn Asn Pro Gln Val Met Asp Thr Glu His Ser Asn 85 90 95 ccc cca gat tctggg tcc tcc gtg ccc acg gat ccc acc tgg ggc cca 456 Pro Pro Asp Ser GlySer Ser Val Pro Thr Asp Pro Thr Trp Gly Pro 100 105 110 gag agg aga ggagag gag tct tca ggg cat ttc ctg gtc gct gcc aca 504 Glu Arg Arg Gly GluGlu Ser Ser Gly His Phe Leu Val Ala Ala Thr 115 120 125 gaa cca gta tgtggc att cct gtc aaa tgg cct gcc cat gaa gcc ctg 552 Glu Pro Val Cys GlyIle Pro Val Lys Trp Pro Ala His Glu Ala Leu 130 135 140 gaa ttc cag ctccac ctc cac tac cac tcc aag cct ggc ccc acc agt 600 Glu Phe Gln Leu HisLeu His Tyr His Ser Lys Pro Gly Pro Thr Ser 145 150 155 160 gct gtt tggcct agg aac tgt ggc tgg gaa ggt gcc tcc aac aat ggg 648 Ala Val Trp ProArg Asn Cys Gly Trp Glu Gly Ala Ser Asn Asn Gly 165 170 175 atc cag ggaagc caa gga gaa gac agc ccc cct cct att tca gcc tcc 696 Ile Gln Gly SerGln Gly Glu Asp Ser Pro Pro Pro Ile Ser Ala Ser 180 185 190 tgc acc caaggc agt gcc tga gaagcccatc atagacaaga agtagcaaac 747 Cys Thr Gln Gly SerAla 195 tgtacattcc ttcttcctcc ccctgctcca gaaggtgccg gtactgaagatgctccagta 807 attggtgacc caaccctagg aagtagggag aaatgaagga agggcataggaaaattttcc 867 cagtaaatcc cctgatggtc acattaaggt aaaggttttg gctggtcagtgtgccaagac 927 ctctccagct tctcattcat gatgacctct caaagttggg aaacaagctgatttcttgcc 987 aagaggtctc ccaggagata tttgggaaat gtgaagttcg tatctttaaggagcattttt 1047 ggtcagcatg gttgatgaac taatgatgag agagttaagg aatgttgctagaacataggg 1107 cttgctggta cctatgtgac taagaaaggg acatgatgta agggaaaaggcctcaaattc 1167 ttgtgaatgt ctggacattc tcgttaatat tcttttgggc taatagtgacatagtgtgca 1227 gaggtgtacc agggatcatg ggggatttcc tagcactagt atgcttctagttttagataa 1287 ctccctcctt tattccctgg ccccttgtat tttccttatc ttcctctttcaagaccccta 1347 cccattttgc ctatccgtag gctggggctt gtgtctttgt cattgtctggttcttaagag 1407 tcccagactt tgggagacca gctccaggtg gcgtcctccc tgcctctccgtcttgtaatg 1467 agttgtagta tttactctta acataggatc atttggaaca ggagttctgaggaggagaga 1527 gtgagggttt tgctattgac tgacttgaac gatggcttct cctcaagctgtaggctccag 1587 agcttcctaa cctagtaaaa tgtcaagaac agacgggaga tattagtgtctttccctcta 1647 tcattaaagg tgttttaacc aaaaaaaaaa aaaaaaaaaa 1687 31 198PRT Homo sapiens 31 Met Ala His Glu Ser Glu Arg Ser Ser Arg Leu Gly ValPro Cys Gly 1 5 10 15 Glu Pro Ala Glu Leu Gly Gly Asp Ala Ser Glu GluAsp His Pro Gln 20 25 30 Val Cys Ala Lys Cys Cys Ala Gln Phe Thr Asp ProThr Glu Phe Leu 35 40 45 Ala His Gln Asn Ala Cys Ser Thr Asp Pro Pro ValMet Val Ile Ile 50 55 60 Gly Gly Gln Glu Asn Pro Asn Asn Ser Ser Ala SerSer Glu Pro Arg 65 70 75 80 Pro Glu Gly His Asn Asn Pro Gln Val Met AspThr Glu His Ser Asn 85 90 95 Pro Pro Asp Ser Gly Ser Ser Val Pro Thr AspPro Thr Trp Gly Pro 100 105 110 Glu Arg Arg Gly Glu Glu Ser Ser Gly HisPhe Leu Val Ala Ala Thr 115 120 125 Glu Pro Val Cys Gly Ile Pro Val LysTrp Pro Ala His Glu Ala Leu 130 135 140 Glu Phe Gln Leu His Leu His TyrHis Ser Lys Pro Gly Pro Thr Ser 145 150 155 160 Ala Val Trp Pro Arg AsnCys Gly Trp Glu Gly Ala Ser Asn Asn Gly 165 170 175 Ile Gln Gly Ser GlnGly Glu Asp Ser Pro Pro Pro Ile Ser Ala Ser 180 185 190 Cys Thr Gln GlySer Ala 195 32 1028 PRT Homo sapiens 32 Pro Leu Gln Arg Tyr Gly His SerLeu Ala Leu Tyr Gln Glu Asn Ile 1 5 10 15 Phe Met Tyr Gly Gly Arg IleGlu Thr Asn Asp Gly Asn Val Thr Asp 20 25 30 Glu Leu Trp Val Phe Asn IleHis Ser Gln Ser Trp Ser Thr Lys Thr 35 40 45 Pro Thr Val Leu Gly His GlyGln Gln Tyr Ala Val Glu Gly His Ser 50 55 60 Ala His Ile Met Glu Leu AspSer Arg Asp Val Val Met Ile Ile Ile 65 70 75 80 Phe Gly Tyr Ser Ala IleTyr Gly Tyr Thr Ser Ser Ile Gln Glu Tyr 85 90 95 His Ile Ser Ser Asn ThrTrp Leu Val Pro Glu Thr Lys Gly Ala Ile 100 105 110 Val Gln Gly Gly TyrGly His Thr Ser Val Tyr Asp Glu Ile Thr Lys 115 120 125 Ser Ile Tyr ValHis Gly Gly Tyr Lys Ala Leu Pro Gly Asn Lys Tyr 130 135 140 Gly Leu ValAsp Asp Leu Tyr Lys Tyr Glu Val Asn Thr Lys Thr Trp 145 150 155 160 ThrIle Leu Lys Glu Ser Gly Phe Ala Arg Tyr Leu His Ser Ala Val 165 170 175Leu Ile Asn Gly Ala Met Leu Ile Phe Gly Gly Asn Thr His Asn Asp 180 185190 Thr Ser Leu Ser Asn Gly Ala Lys Cys Phe Ser Ala Asp Phe Leu Ala 195200 205 Tyr Asp Ile Ala Cys Asp Glu Trp Lys Ile Leu Pro Lys Pro Asn Leu210 215 220 His Arg Asp Val Asn Arg Phe Gly His Ser Ala Val Val Ile AsnGly 225 230 235 240 Ser Met Tyr Ile Phe Gly Gly Phe Ser Ser Val Leu LeuAsn Asp Ile 245 250 255 Leu Val Tyr Lys Pro Pro Asn Cys Lys Ala Phe ArgAsp Glu Glu Leu 260 265 270 Cys Lys Asn Ala Gly Pro Gly Ile Lys Cys ValTrp Asn Lys Asn His 275 280 285 Cys Glu Ser Trp Glu Ser Gly Asn Thr AsnAsn Ile Leu Arg Ala Lys 290 295 300 Cys Pro Pro Lys Thr Ala Ala Ser AspAsp Arg Cys Tyr Arg Tyr Ala 305 310 315 320 Asp Cys Ala Ser Cys Thr AlaAsn Thr Asn Gly Cys Gln Trp Cys Asp 325 330 335 Asp Lys Lys Cys Ile SerAla Asn Ser Asn Cys Ser Met Ser Val Lys 340 345 350 Asn Tyr Thr Lys CysHis Val Arg Asn Glu Gln Ile Cys Asn Lys Leu 355 360 365 Thr Ser Cys LysSer Cys Ser Leu Asn Leu Asn Cys Gln Trp Asp Gln 370 375 380 Arg Gln GlnGlu Cys Gln Ala Leu Pro Ala His Leu Cys Gly Glu Gly 385 390 395 400 TrpSer His Ile Gly Asp Ala Cys Leu Arg Val Asn Ser Ser Arg Glu 405 410 415Asn Tyr Asp Asn Ala Lys Leu Tyr Cys Tyr Asn Leu Ser Gly Asn Leu 420 425430 Ala Ser Leu Thr Thr Ser Lys Glu Val Glu Phe Val Leu Asp Glu Ile 435440 445 Gln Lys Tyr Thr Gln Gln Lys Val Ser Pro Trp Val Gly Leu Arg Lys450 455 460 Ile Asn Ile Ser Tyr Trp Gly Trp Glu Asp Met Ser Pro Phe ThrAsn 465 470 475 480 Thr Thr Leu Gln Trp Leu Pro Gly Glu Pro Asn Asp SerGly Phe Cys 485 490 495 Ala Tyr Leu Glu Arg Ala Ala Val Ala Gly Leu LysAla Asn Pro Cys 500 505 510 Thr Ser Met Ala Asn Gly Leu Val Cys Glu LysPro Val Val Ser Pro 515 520 525 Asn Gln Asn Ala Arg Pro Cys Lys Lys ProCys Ser Leu Arg Thr Ser 530 535 540 Cys Ser Asn Cys Thr Ser Asn Gly MetGlu Cys Met Trp Cys Ser Ser 545 550 555 560 Thr Lys Arg Cys Val Asp SerAsn Ala Tyr Ile Ile Ser Phe Pro Tyr 565 570 575 Gly Gln Cys Leu Glu TrpGln Thr Ala Thr Cys Ser Pro Gln Asn Cys 580 585 590 Ser Gly Leu Arg ThrCys Gly Gln Cys Leu Glu Gln Pro Gly Cys Gly 595 600 605 Trp Cys Asn AspPro Ser Asn Thr Gly Arg Gly His Cys Ile Glu Gly 610 615 620 Ser Ser ArgGly Pro Met Lys Leu Ile Gly Met His His Asn Glu Met 625 630 635 640 ValLeu Asp Thr Asn Leu Cys Pro Lys Glu Lys Asn Tyr Glu Trp Ser 645 650 655Phe Ile Gln Cys Pro Ala Cys Gln Cys Asn Gly His Ser Thr Cys Ile 660 665670 Asn Asn Asn Val Cys Glu Gln Cys Lys Asn Leu Thr Thr Gly Lys Gln 675680 685 Cys Gln Asp Cys Met Pro Gly Tyr Tyr Gly Asp Pro Thr Asn Gly Gly690 695 700 Gln Cys Thr Ala Cys Thr Cys Ser Gly His Ala Asn Ile Cys HisLeu 705 710 715 720 His Thr Gly Lys Cys Phe Cys Thr Thr Lys Gly Ile LysGly Asp Gln 725 730 735 Cys Gln Leu Cys Asp Ser Glu Asn Arg Tyr Val GlyAsn Pro Leu Arg 740 745 750 Gly Thr Cys Tyr Tyr Ser Leu Leu Ile Asp TyrGln Phe Thr Phe Ser 755 760 765 Leu Leu Gln Glu Asp Asp Arg His His ThrAla Ile Asn Phe Ile Ala 770 775 780 Asn Pro Glu Gln Ser Asn Lys Asn LeuAsp Ile Ser Ile Asn Ala Ser 785 790 795 800 Asn Asn Phe Asn Leu Asn IleThr Trp Ser Val Gly Ser Thr Ala Gly 805 810 815 Thr Ile Ser Gly Glu GluThr Ser Ile Val Ser Lys Asn Asn Ile Lys 820 825 830 Glu Tyr Arg Asp SerPhe Ser Tyr Glu Lys Phe Asn Phe Arg Ser Asn 835 840 845 Pro Asn Ile ThrPhe Tyr Val Tyr Val Ser Asn Phe Ser Trp Pro Ile 850 855 860 Lys Ile GlnIle Ala Phe Ser Gln His Asn Thr Ile Met Asp Leu Val 865 870 875 880 GlnPhe Phe Val Thr Phe Phe Ser Cys Phe Leu Ser Leu Leu Leu Val 885 890 895Ala Ala Val Val Trp Lys Ile Lys Gln Thr Cys Trp Ala Ser Arg Arg 900 905910 Arg Glu Gln Leu Leu Arg Glu Arg Gln Gln Met Ala Ser Arg Pro Phe 915920 925 Ala Ser Val Asp Val Ala Leu Glu Val Gly Ala Glu Gln Thr Glu Phe930 935 940 Leu Arg Gly Pro Leu Glu Gly Ala Pro Lys Pro Ile Ala Ile GluPro 945 950 955 960 Cys Ala Gly Asn Arg Ala Ala Val Leu Thr Val Phe LeuCys Leu Pro 965 970 975 Arg Gly Ser Ser Gly Ala Pro Pro Pro Gly Gln SerGly Leu Ala Ile 980 985 990 Ala Ser Ala Leu Ile Asp Ile Ser Gln Gln LysAla Ser Asp Ser Lys 995 1000 1005 Asp Lys Thr Ser Gly Val Arg Asn ArgLys His Leu Ser Thr Arg 1010 1015 1020 Gln Gly Thr Cys Val 1025 33 1339PRT Homo sapiens 33 Lys Thr Ala Leu Leu Leu His Gly Val Phe Leu Leu LeuLeu Ile Phe 1 5 10 15 Phe Leu Glu Gln Gly Lys Gly Asn Leu His Val ThrSer Pro Glu Asp 20 25 30 Ala Glu Cys Arg Arg Thr Lys Glu Arg Leu Ser AsnGly Asn Ser Arg 35 40 45 Gly Ser Val Ser Lys Ser Ser Arg Asn Ile Pro ArgArg His Thr Leu 50 55 60 Gly Gly Pro Arg Ser Ser Lys Glu Ile Leu Gly MetGln Thr Ser Glu 65 70 75 80 Met Asp Arg Lys Arg Glu Ala Phe Leu Glu HisLeu Lys Gln Lys Tyr 85 90 95 Pro His His Ala Ser Ala Ile Met Gly His GlnGlu Arg Leu Arg Asp 100 105 110 Gln Thr Arg Ser Pro Lys Leu Ser His SerPro Gln Pro Pro Ser Leu 115 120 125 Gly Asp Pro Val Glu His Leu Ser GluThr Ser Ala Asp Ser Leu Glu 130 135 140 Ala Met Ser Glu Gly Asp Ala ProThr Pro Phe Ser Arg Gly Ser Arg 145 150 155 160 Thr Arg Ala Ser Leu ProVal Val Arg Ser Thr Asn Gln Thr Lys Glu 165 170 175 Arg Ser Leu Gly ValLeu Tyr Leu Gln Tyr Gly Asp Glu Thr Lys Gln 180 185 190 Leu Arg Met ProAsn Glu Ile Thr Ser Ala Asp Thr Ile Arg Ala Leu 195 200 205 Phe Val SerAla Phe Pro Gln Gln Leu Thr Met Lys Met Leu Glu Ser 210 215 220 Pro SerVal Ala Ile Tyr Ile Lys Asp Glu Ser Arg Asn Val Tyr Tyr 225 230 235 240Glu Leu Asn Asp Val Arg Asn Ile Gln Asp Arg Ser Leu Leu Lys Val 245 250255 Tyr Asn Lys Asp Pro Ala His Ala Phe Asn His Thr Pro Lys Thr Met 260265 270 Asn Gly Asp Met Arg Met Gln Arg Glu Leu Val Tyr Ala Arg Gly Asp275 280 285 Gly Pro Gly Ala Pro Arg Pro Gly Ser Thr Ala His Pro Pro HisAla 290 295 300 Ile Pro Asn Ser Pro Pro Ser Thr Pro Val Pro His Ser MetPro Pro 305 310 315 320 Ser Pro Ser Arg Ile Pro Tyr Gly Gly Thr Arg SerMet Val Val Pro 325 330 335 Gly Asn Ala Thr Ile Pro Arg Asp Arg Ile SerSer Leu Pro Val Ser 340 345 350 Arg Pro Ile Ser Pro Ser Pro Ser Ala IleLeu Glu Arg Arg Asp Val 355 360 365 Lys Pro Asp Glu Asp Met Ser Gly LysAsn Ile Ala Met Tyr Arg Asn 370 375 380 Glu Gly Phe Tyr Ala Asp Pro TyrLeu Tyr His Glu Gly Arg Met Ser 385 390 395 400 Ile Ala Ser Ser His GlyGly His Pro Leu Asp Val Pro Asp His Ile 405 410 415 Ile Ala Tyr His ArgThr Ala Ile Arg Ser Ala Ser Ala Tyr Cys Asn 420 425 430 Pro Ser Met GlnAla Glu Met His Met Glu Gln Ser Leu Tyr Arg Gln 435 440 445 Lys Ser ArgLys Tyr Pro Asp Ser His Leu Pro Thr Leu Gly Ser Lys 450 455 460 Thr ProPro Ala Ser Pro His Arg Val Ser Asp Leu Arg Met Ile Asp 465 470 475 480Met His Ala His Tyr Asn Ala His Gly Pro Pro His Thr Met Gln Pro 485 490495 Asp Arg Ala Ser Pro Ser Arg Gln Ala Phe Lys Lys Glu Pro Gly Thr 500505 510 Leu Val Tyr Ile Glu Lys Pro Arg Ser Ala Ala Gly Leu Ser Ser Leu515 520 525 Val Asp Leu Gly Pro Pro Leu Met Glu Lys Gln Val Phe Ala TyrSer 530 535 540 Thr Ala Thr Ile Pro Lys Asp Arg Glu Thr Arg Glu Arg MetGln Ala 545 550 555 560 Met Glu Lys Gln Ile Ala Ser Leu Thr Gly Leu ValGln Ser Ala Leu 565 570 575 Phe Lys Gly Pro Ile Thr Ser Tyr Ser Lys AspAla Ser Ser Glu Lys 580 585 590 Met Met Lys Thr Thr Ala Asn Arg Asn HisThr Asp Ser Ala Gly Thr 595 600 605 Pro His Val Ser Gly Gly Lys Met LeuSer Ala Leu Glu Ser Thr Val 610 615 620 Pro Pro Ser Gln Pro Pro Pro ValGly Thr Ser Ala Ile His Met Ser 625 630 635 640 Leu Leu Glu Met Arg ArgSer Val Ala Glu Leu Arg Leu Gln Leu Gln 645 650 655 Gln Met Arg Gln LeuGln Leu Gln Asn Gln Glu Leu Leu Arg Ala Met 660 665 670 Met Lys Lys AlaGlu Leu Glu Ile Ser Gly Lys Val Met Glu Thr Met 675 680 685 Lys Arg LeuGlu Asp Pro Val Gln Arg Gln Arg Val Leu Val Glu Gln 690 695 700 Glu ArgGln Lys Tyr Leu His Glu Glu Glu Lys Ile Val Lys Lys Leu 705 710 715 720Cys Glu Leu Glu Asp Phe Val Glu Asp Leu Lys Lys Asp Ser Thr Ala 725 730735 Ala Ser Arg Leu Val Thr Leu Lys Asp Val Glu Asp Gly Ala Phe Leu 740745 750 Leu Arg Gln Val Gly Glu Ala Val Ala Thr Leu Lys Gly Glu Phe Pro755 760 765 Thr Leu Gln Asn Lys Met Arg Ala Ile Leu Arg Ile Glu Val GluAla 770 775 780 Val Arg Phe Leu Lys Glu Glu Pro His Lys Leu Asp Ser LeuLeu Lys 785 790 795 800 Arg Val Arg Ser Met Thr Asp Val Leu Thr Met LeuArg Arg His Val 805 810 815 Thr Asp Gly Leu Leu Lys Gly Thr Asp Ala AlaGln Ala Ala Gln Tyr 820 825 830 Met Ala Met Glu Lys Ala Thr Ala Ala GluVal Leu Lys Ser Gln Glu 835 840 845 Glu Ala Ala His Thr Ser Gly Gln ProPhe His Ser Thr Gly Ala Pro 850 855 860 Gly Asp Ala Lys Ser Glu Val ValPro Leu Ser Gly Met Met Val Arg 865 870 875 880 His Ala Gln Ser Ser ProVal Val Ile Gln Pro Ser Gln His Ser Val 885 890 895 Ala Leu Leu Asn ProAla Gln Asn Leu Pro His Val Ala Ser Ser Pro 900 905 910 Ala Val Pro GlnGlu Ala Thr Ser Thr Leu Gln Met Ser Gln Ala Pro 915 920 925 Gln Ser ProGln Ile Pro Met Asn Gly Ser Ala Met Gln Ser Leu Phe 930 935 940 Ile GluGlu Ile His Ser Val Ser Ala Lys Asn Arg Ala Val Ser Ile 945 950 955 960Glu Lys Ala Glu Lys Lys Trp Glu Glu Lys Arg Gln Asn Leu Asp His 965 970975 Tyr Asn Gly Lys Glu Phe Glu Lys Leu Leu Glu Glu Ala Gln Ala Asn 980985 990 Ile Met Lys Ser Ile Pro Asn Leu Glu Met Pro Pro Ala Thr Gly Pro995 1000 1005 Leu Pro Arg Gly Asp Ala Pro Val Asp Lys Val Glu Leu SerGlu 1010 1015 1020 Asp Ser Pro Asn Ser Glu Gln Asp Leu Glu Lys Leu GlyGly Lys 1025 1030 1035 Ser Pro Pro Pro Pro Pro Pro Pro Pro Arg Arg SerTyr Leu Pro 1040 1045 1050 Gly Ser Gly Leu Thr Thr Thr Arg Ser Gly AspVal Val Tyr Thr 1055 1060 1065 Gly Arg Lys Glu Asn Ile Thr Ala Lys AlaSer Ser Glu Asp Ala 1070 1075 1080 Gly Pro Ser Pro Gln Thr Arg Ala ThrLys Tyr Pro Ala Glu Glu 1085 1090 1095 Pro Ala Ser Ala Trp Thr Pro SerPro Pro Pro Val Thr Thr Ser 1100 1105 1110 Ser Ser Lys Asp Glu Glu GluGlu Glu Glu Glu Gly Asp Lys Ile 1115 1120 1125 Met Ala Glu Leu Gln GlySer Ser Gly Ala Pro Gln Thr Ser Arg 1130 1135 1140 Met Pro Val Pro MetSer Ala Lys Asn Arg Pro Gly Thr Leu Asp 1145 1150 1155 Lys Pro Gly LysGln Ser Lys Leu Gln Asp Pro Arg Gln Tyr Arg 1160 1165 1170 Gln Ala AsnGly Ser Ala Lys Lys Ser Gly Gly Asp Phe Lys Pro 1175 1180 1185 Thr SerPro Ser Leu Pro Ala Ser Lys Ile Pro Ala Leu Ser Pro 1190 1195 1200 SerSer Gly Lys Ser Ser Ser Leu Pro Ser Ser Ser Gly Asp Ser 1205 1210 1215Ser Asn Leu Pro Asn Pro Pro Ala Thr Lys Pro Ser Ile Ala Ser 1220 12251230 Asn Pro Leu Ser Pro Gln Thr Gly Pro Pro Ala His Ser Ala Ser 12351240 1245 Leu Ile Pro Ser Val Ser Asn Gly Ser Leu Lys Phe Gln Ser Leu1250 1255 1260 Thr His Thr Gly Lys Gly His His Leu Ser Phe Ser Pro GlnSer 1265 1270 1275 Gln Asn Gly Arg Ala Pro Pro Pro Leu Ser Phe Ser SerSer Pro 1280 1285 1290 Pro Ser Pro Ala Ser Ser Val Ser Leu Asn Gln GlyAla Lys Gly 1295 1300 1305 Thr Arg Thr Ile His Thr Pro Ser Leu Thr SerTyr Lys Ala Gln 1310 1315 1320 Asn Gly Ser Ser Ser Lys Ala Thr Pro SerThr Ala Lys Glu Thr 1325 1330 1335 Ser 34 1973 PRT Homo sapiens 34 MetLeu Ile His Gln Gln Leu Cys Leu Asn Phe Ala Arg Ser Leu Trp 1 5 10 15Tyr Gln Gln Thr Leu Pro Pro His Glu Ala Lys His Tyr Leu Ser Leu 20 25 30Phe Leu Ser Cys Tyr Gln Thr Gly Ala Ser Leu Val Thr His Phe Tyr 35 40 45Pro Leu Met Gly Val Glu Leu Asn Asp Arg Leu Leu Gly Ser Gln Leu 50 55 60Leu Ala Cys Thr Leu Ser His Asn Thr Leu Phe Gly Glu Ala Pro Ser 65 70 7580 Asp Leu Met Val Lys Pro Asp Gly Pro Tyr Asp Phe Tyr Gln His Pro 85 9095 Asn Val Pro Glu Ala Arg Gln Cys Gln Pro Val Leu Gln Gly Phe Ser 100105 110 Glu Ala Val Ser His Leu Leu Gln Asp Trp Pro Glu His Pro Ala Leu115 120 125 Glu Gln Leu Leu Val Val Met Asp Arg Ile Arg Ser Phe Pro LeuSer 130 135 140 Ser Pro Ile Ser Lys Phe Leu Asn Gly Leu Glu Ile Leu LeuAla Lys 145 150 155 160 Ala Gln Asp Trp Glu Glu Asn Ala Ser Arg Ala LeuSer Leu Arg Lys 165 170 175 His Leu Asp Leu Ile Ser Gln Met Ile Ile ArgTrp Arg Lys Leu Glu 180 185 190 Leu Asn Cys Trp Ser Met Ser Leu Asp AsnThr Met Lys Arg His Thr 195 200 205 Glu Lys Ser Thr Lys His Trp Phe SerIle Tyr Gln Met Leu Glu Lys 210 215 220 His Met Gln Glu Gln Thr Glu GluGln Glu Asp Asp Lys Gln Met Thr 225 230 235 240 Leu Met Leu Leu Val SerThr Leu Gln Ala Phe Ile Glu Gly Ser Ser 245 250 255 Leu Gly Glu Phe HisVal Arg Leu Gln Met Leu Leu Val Phe His Cys 260 265 270 His Val Leu LeuMet Pro Gln Val Glu Gly Lys Asp Ser Leu Cys Ser 275 280 285 Val Leu TrpAsn Leu Tyr His Tyr Tyr Lys Gln Phe Phe Asp Arg Val 290 295 300 Gln AlaLys Ile Val Glu Leu Arg Ser Pro Leu Glu Lys Glu Leu Lys 305 310 315 320Glu Phe Val Lys Ile Ser Lys Trp Asn Asp Val Ser Phe Trp Ser Ile 325 330335 Lys Gln Ser Val Glu Lys Thr His Arg Thr Leu Phe Lys Phe Met Lys 340345 350 Lys Phe Glu Ala Val Leu Ser Glu Pro Cys Arg Ser Ser Leu Val Glu355 360 365 Ser Asp Lys Glu Glu Gln Pro Asp Phe Leu Pro Arg Pro Thr AspGly 370 375 380 Ala Ala Ser Glu Leu Ser Ser Ile Gln Asn Leu Asn Arg AlaLeu Arg 385 390 395 400 Glu Thr Leu Leu Ala Gln Pro Ala Ala Gly Gln AlaThr Ile Pro Glu 405 410 415 Trp Cys Gln Gly Ala Ala Pro Ser Gly Leu GluGly Glu Leu Leu Arg 420 425 430 Arg Leu Pro Lys Leu Arg Lys Arg Met ArgLys Met Cys Leu Thr Phe 435 440 445 Met Lys Glu Ser Pro Leu Pro Arg LeuVal Glu Gly Leu Asp Gln Phe 450 455 460 Thr Gly Glu Val Ile Ser Ser ValSer Glu Leu Gln Ser Leu Lys Val 465 470 475 480 Glu Pro Ser Ala Glu LysGlu Lys Gln Arg Ser Glu Ala Lys His Ile 485 490 495 Leu Met Gln Lys GlnArg Ala Leu Ser Asp Leu Phe Lys His Leu Ala 500 505 510 Lys Ile Gly LeuSer Tyr Arg Lys Gly Leu Ala Trp Ala Arg Ser Lys 515 520 525 Asn Pro GlnGlu Met Leu His Leu His Pro Leu Asp Leu Gln Ser Ala 530 535 540 Leu SerIle Val Ser Ser Thr Gln Glu Ala Asp Ser Arg Leu Leu Thr 545 550 555 560Glu Ile Ser Ser Ser Trp Asp Gly Cys Gln Lys Tyr Phe Tyr Arg Ser 565 570575 Leu Ala Arg His Ala Arg Leu Asn Ala Ala Leu Ala Thr Pro Ala Lys 580585 590 Glu Met Gly Met Gly Asn Val Glu Arg Cys Arg Gly Phe Ser Ala His595 600 605 Leu Met Lys Met Leu Val Arg Gln Arg Arg Ser Leu Thr Thr LeuSer 610 615 620 Glu Gln Trp Ile Ile Leu Arg Asn Leu Leu Ser Cys Val GlnGlu Ile 625 630 635 640 His Ser Arg Leu Met Gly Pro Gln Ala Tyr Pro ValAla Phe Pro Pro 645 650 655 Gln Asp Gly Val Gln Gln Trp Thr Glu Arg LeuGln His Leu Ala Met 660 665 670 Gln Cys Gln Ile Leu Leu Glu Gln Leu SerTrp Leu Leu Gln Cys Cys 675 680 685 Pro Ser Val Gly Pro Ala Pro Gly HisGly Asn Val Gln Val Leu Gly 690 695 700 Gln Pro Pro Gly Pro Cys Leu GluGly Pro Glu Leu Ser Lys Gly Gln 705 710 715 720 Leu Cys Gly Val Val LeuAsp Leu Ile Pro Ser Asn Leu Ser Tyr Pro 725 730 735 Ser Pro Ile Pro GlySer Gln Leu Pro Ser Gly Cys Arg Met Arg Lys 740 745 750 Gln Asp His LeuTrp Gln Gln Ser Thr Thr Arg Leu Thr Glu Met Leu 755 760 765 Lys Thr IleLys Thr Val Lys Ala Asp Val Asp Lys Ile Arg Gln Gln 770 775 780 Ser CysGlu Thr Leu Phe His Ser Trp Lys Asp Phe Glu Val Cys Ser 785 790 795 800Ser Ala Leu Ser Cys Leu Ser Gln Val Ser Val His Leu Gln Gly Leu 805 810815 Glu Ser Leu Phe Ile Leu Pro Gly Met Glu Val Glu Gln Arg Asp Ser 820825 830 Gln Met Ala Leu Val Glu Ser Leu Glu Tyr Val Arg Gly Glu Ile Ser835 840 845 Lys Ala Met Ala Asp Phe Thr Thr Trp Lys Thr His Leu Leu ThrSer 850 855 860 Asp Ser Gln Gly Gly Asn Gln Met Leu Asp Glu Gly Phe ValGlu Asp 865 870 875 880 Phe Ser Glu Gln Met Glu Ile Ala Ile Arg Ala IleLeu Cys Ala Ile 885 890 895 Gln Asn Leu Glu Glu Arg Lys Asn Glu Lys AlaGlu Glu Asn Thr Asp 900 905 910 Gln Ala Ser Pro Gln Glu Asp Tyr Ala GlyPhe Glu Arg Leu Gln Ser 915 920 925 Gly His Leu Thr Lys Leu Leu Glu AspAsp Phe Trp Ala Asp Val Ser 930 935 940 Thr Leu His Val Gln Lys Ile IleSer Ala Ile Ser Glu Leu Leu Glu 945 950 955 960 Arg Leu Lys Ser Tyr GlyGlu Asp Gly Thr Ala Ala Lys His Leu Phe 965 970 975 Phe Ser Gln Ser CysSer Leu Leu Val Arg Leu Val Pro Val Leu Ser 980 985 990 Ser Tyr Ser AspLeu Val Leu Phe Phe Leu Thr Met Ser Leu Ala Thr 995 1000 1005 His ArgSer Thr Ala Lys Leu Leu Ser Val Leu Ala Gln Val Phe 1010 1015 1020 ThrGlu Leu Ala Gln Lys Gly Phe Cys Leu Pro Lys Glu Phe Met 1025 1030 1035Glu Asp Ser Ala Gly Glu Gly Ala Thr Glu Phe His Asp Tyr Glu 1040 10451050 Gly Gly Gly Ile Gly Glu Gly Glu Gly Met Lys Asp Val Ser Asp 10551060 1065 Gln Ile Gly Asn Glu Glu Gln Val Glu Asp Thr Phe Gln Lys Gly1070 1075 1080 Gln Glu Lys Asp Lys Glu Asp Pro Asp Ser Lys Ser Asp IleLys 1085 1090 1095 Gly Glu Asp Asn Ala Ile Glu Met Ser Glu Asp Phe AspGly Lys 1100 1105 1110 Met His Asp Gly Glu Leu Glu Glu Gln Glu Glu AspAsp Glu Lys 1115 1120 1125 Ser Asp Ser Glu Gly Gly Asp Leu Asp Lys HisMet Gly Asp Leu 1130 1135 1140 Asn Gly Glu Glu Ala Asp Lys Leu Asp GluArg Leu Trp Gly Asp 1145 1150 1155 Asp Asp Glu Glu Glu Asp Glu Glu GluGlu Asp Asn Lys Thr Glu 1160 1165 1170 Glu Thr Gly Pro Gly Met Asp GluGlu Asp Ser Glu Leu Val Ala 1175 1180 1185 Lys Asp Asp Asn Leu Asp SerGly Asn Ser Asn Lys Asp Lys Ser 1190 1195 1200 Gln Gln Asp Lys Lys GluGlu Lys Glu Glu Ala Glu Ala Asp Asp 1205 1210 1215 Gly Gly Gln Gly GluAsp Lys Ile Asn Glu Gln Ile Asp Glu Arg 1220 1225 1230 Asp Tyr Asp GluAsn Glu Val Asp Pro Tyr His Gly Asn Gln Glu 1235 1240 1245 Lys Val ProGlu Pro Glu Ala Leu Asp Leu Pro Asp Asp Leu Asn 1250 1255 1260 Leu AspSer Glu Asp Lys Asn Gly Gly Glu Asp Thr Asp Asn Glu 1265 1270 1275 GluGly Glu Glu Glu Asn Pro Leu Glu Ile Lys Glu Lys Pro Glu 1280 1285 1290Glu Ala Gly His Glu Ala Glu Glu Arg Gly Glu Thr Glu Thr Asp 1295 13001305 Gln Asn Glu Ser Gln Ser Pro Gln Glu Pro Glu Glu Gly Pro Ser 13101315 1320 Glu Asp Asp Lys Ala Glu Gly Glu Glu Glu Met Asp Thr Gly Ala1325 1330 1335 Asp Asp Gln Asp Gly Asp Ala Ala Gln His Pro Glu Glu HisSer 1340 1345 1350 Glu Glu Gln Gln Gln Ser Val Glu Glu Lys Asp Lys GluAla Asp 1355 1360 1365 Glu Glu Gly Gly Glu Asn Gly Pro Ala Asp Gln GlyPhe Gln Pro 1370 1375 1380 Gln Glu Glu Glu Glu Arg Glu Asp Ser Asp ThrGlu Glu Gln Val 1385 1390 1395 Pro Glu Ala Leu Glu Arg Lys Glu His AlaSer Cys Gly Gln Thr 1400 1405 1410 Gly Val Glu Asn Met Gln Asn Thr GlnAla Met Glu Leu Ala Gly 1415 1420 1425 Ala Ala Pro Glu Lys Glu Gln GlyLys Glu Glu His Gly Ser Gly 1430 1435 1440 Ala Ala Asp Ala Asn Gln AlaGlu Gly His Glu Ser Asn Phe Ile 1445 1450 1455 Ala Gln Leu Ala Ser GlnLys His Thr Arg Lys Asn Thr Gln Ser 1460 1465 1470 Phe Lys Arg Lys ProGly Gln Ala Asp Asn Glu Arg Ser Met Gly 1475 1480 1485 Asp His Asn GluArg Val His Lys Arg Leu Arg Thr Val Asp Thr 1490 1495 1500 Asp Ser HisAla Glu Gln Gly Pro Ala Gln Gln Pro Gln Ala Gln 1505 1510 1515 Val GluAsp Ala Asp Ala Phe Glu His Ile Lys Gln Gly Ser Asp 1520 1525 1530 AlaTyr Asp Ala Gln Thr Tyr Asp Val Ala Ser Lys Glu Gln Gln 1535 1540 1545Gln Ser Ala Lys Asp Ser Gly Lys Asp Gln Glu Glu Glu Glu Ile 1550 15551560 Glu Asp Thr Leu Met Asp Thr Glu Glu Gln Glu Glu Phe Lys Ala 15651570 1575 Ala Asp Val Glu Gln Leu Lys Pro Glu Glu Ile Lys Ser Gly Thr1580 1585 1590 Thr Ala Pro Leu Gly Phe Asp Glu Met Glu Val Glu Ile GlnThr 1595 1600 1605 Val Lys Thr Glu Glu Asp Gln Asp Pro Arg Thr Asp LysAla His 1610 1615 1620 Lys Glu Thr Glu Asn Glu Lys Pro Glu Arg Ser ArgGlu Ser Thr 1625 1630 1635 Ile His Thr Ala His Gln Phe Leu Met Asp ThrIle Phe Gln Pro 1640 1645 1650 Phe Leu Lys Asp Val Asn Glu Leu Arg GlnGlu Leu Glu Arg Gln 1655 1660 1665 Leu Glu Met Trp Gln Pro Arg Glu SerGly Asn Pro Glu Glu Glu 1670 1675 1680 Lys Val Ala Ala Glu Met Trp GlnSer Tyr Leu Ile Leu Thr Ala 1685 1690 1695 Pro Leu Ser Gln Arg Leu CysGlu Glu Leu Arg Leu Ile Leu Glu 1700 1705 1710 Pro Thr Gln Ala Ala LysLeu Lys Gly Asp Tyr Arg Thr Gly Lys 1715 1720 1725 Arg Leu Asn Ile ArgLys Val Ile Pro Tyr Ile Ala Ser Gln Phe 1730 1735 1740 Arg Lys Asp LysIle Trp Leu Arg Arg Thr Lys Pro Ser Lys Arg 1745 1750 1755 Gln Tyr GlnIle Cys Leu Ala Ile Asp Asp Ser Ser Ser Met Val 1760 1765 1770 Asp AsnHis Thr Lys Gln Leu Ala Phe Glu Ser Leu Ala Val Ile 1775 1780 1785 GlyAsn Ala Leu Thr Leu Leu Glu Val Gly Gln Ile Ala Val Cys 1790 1795 1800Ser Phe Gly Glu Ser Val Lys Leu Leu His Pro Phe His Glu Gln 1805 18101815 Phe Ser Asp Tyr Ser Gly Ser Gln Ile Leu Arg Leu Cys Lys Phe 18201825 1830 Gln Gln Lys Lys Thr Lys Ile Ala Gln Phe Leu Glu Ser Val Ala1835 1840 1845 Asn Met Phe Ala Ala Ala Gln Gln Leu Ser Gln Asn Ile SerSer 1850 1855 1860 Glu Thr Ala Gln Leu Leu Leu Val Val Ser Asp Gly ArgGly Leu 1865 1870 1875 Phe Leu Glu Gly Lys Glu Arg Val Leu Ala Ala ValGln Ala Ala 1880 1885 1890 Arg Asn Ala Asn Ile Phe Val Ile Phe Val ValLeu Asp Asn Pro 1895 1900 1905 Ser Ser Arg Asp Ser Ile Leu Asp Ile LysVal Pro Ile Phe Lys 1910 1915 1920 Gly Pro Gly Glu Met Pro Glu Ile ArgSer Tyr Met Glu Glu Phe 1925 1930 1935 Pro Phe Pro Tyr Tyr Ile Ile LeuArg Asp Val Asn Ala Leu Pro 1940 1945 1950 Glu Thr Leu Ser Asp Ala LeuArg Gln Trp Phe Glu Leu Val Thr 1955 1960 1965 Ala Ser Asp His Pro 197035 1356 PRT Homo sapiens 35 Met Cys Glu Pro Gln Thr Leu Cys His Ile LeuGly Phe Lys Phe Lys 1 5 10 15 Phe Tyr Gln Glu Pro Asn Gly Glu Thr ProSer Ser Leu Tyr Arg Val 20 25 30 Ala Ala Val Leu Leu Gln Phe Asn Leu IleAsp Leu Asp Asp Leu Tyr 35 40 45 Val His Leu Leu Pro Ala Asp Asn Cys IleMet Asp Glu His Lys Arg 50 55 60 Glu Ile Ala Glu Ala Lys Gln Ile Val ArgLys Leu Thr Met Val Val 65 70 75 80 Leu Ser Ser Glu Lys Met Asp Glu ArgGlu Lys Glu Lys Glu Lys Glu 85 90 95 Glu Glu Lys Val Glu Lys Pro Pro AspAsn Gln Lys Leu Gly Leu Leu 100 105 110 Glu Ala Leu Leu Lys Ile Gly AspTrp Gln His Ala Gln Asn Ile Met 115 120 125 Asp Gln Met Pro Pro Tyr TyrAla Ala Ser His Lys Leu Ile Ala Leu 130 135 140 Ala Ile Cys Lys Leu IleHis Ile Thr Ile Glu Pro Leu Tyr Arg Arg 145 150 155 160 Val Gly Val ProLys Gly Ala Lys Gly Ser Pro Val Asn Ala Leu Gln 165 170 175 Asn Lys ArgAla Pro Lys Gln Ala Glu Ser Phe Glu Asp Leu Arg Arg 180 185 190 Asp ValPhe Asn Met Phe Cys Tyr Leu Gly Pro His Leu Ser His Asp 195 200 205 ProIle Leu Phe Ala Lys Val Val Arg Ile Gly Lys Ser Phe Met Lys 210 215 220Glu Phe Gln Ser Asp Gly Ser Lys Gln Glu Asp Lys Glu Lys Thr Glu 225 230235 240 Val Ile Leu Ser Cys Leu Leu Ser Ile Thr Asp Gln Val Leu Leu Pro245 250 255 Ser Leu Ser Leu Met Asp Cys Asn Ala Cys Met Ser Glu Glu LeuTrp 260 265 270 Gly Met Phe Lys Thr Phe Pro Tyr Gln His Arg Tyr Arg LeuTyr Gly 275 280 285 Gln Trp Lys Asn Glu Thr Tyr Asn Ser His Pro Leu LeuVal Lys Val 290 295 300 Lys Ala Gln Thr Ile Asp Arg Ala Lys Tyr Ile MetLys Arg Leu Thr 305 310 315 320 Lys Glu Asn Val Lys Pro Ser Gly Arg GlnIle Gly Lys Leu Ser His 325 330 335 Ser Asn Pro Thr Ile Leu Phe Asp TyrIle Leu Ser Gln Ile Gln Lys 340 345 350 Tyr Asp Asn Leu Ile Thr Pro ValVal Asp Ser Leu Lys Tyr Leu Thr 355 360 365 Ser Leu Asn Tyr Asp Val LeuAla Tyr Cys Ile Ile Glu Ala Leu Ala 370 375 380 Asn Pro Glu Lys Glu ArgMet Lys His Asp Asp Thr Thr Ile Ser Ser 385 390 395 400 Trp Leu Gln SerLeu Ala Ser Phe Cys Gly Ala Val Phe Arg Lys Tyr 405 410 415 Pro Ile AspLeu Ala Gly Leu Leu Gln Tyr Val Ala Asn Gln Leu Lys 420 425 430 Ala GlyLys Ser Phe Asp Leu Leu Ile Leu Lys Glu Val Val Gln Lys 435 440 445 MetAla Gly Ile Glu Ile Thr Glu Glu Met Thr Met Glu Gln Leu Glu 450 455 460Ala Met Thr Gly Gly Glu Gln Leu Lys Ala Glu Gly Gly Tyr Phe Gly 465 470475 480 Gln Ile Arg Asn Thr Lys Lys Ser Ser Gln Arg Leu Lys Asp Ala Leu485 490 495 Leu Asp His Asp Leu Ala Leu Pro Leu Cys Leu Leu Met Ala GlnGln 500 505 510 Arg Asn Gly Val Ile Phe Gln Glu Gly Gly Glu Lys His LeuLys Leu 515 520 525 Val Gly Lys Leu Tyr Asp Gln Cys His Asp Thr Leu ValGln Phe Gly 530 535 540 Gly Phe Leu Ala Ser Asn Leu Ser Thr Glu Asp TyrIle Lys Arg Val 545 550 555 560 Pro Ser Ile Asp Val Leu Cys Asn Glu PheHis Thr Pro His Asp Ala 565 570 575 Ala Phe Phe Leu Ser Arg Pro Met TyrAla His His Ile Ser Ser Lys 580 585 590 Tyr Asp Glu Leu Lys Lys Ser GluLys Gly Ser Lys Gln Gln His Lys 595 600 605 Val His Lys Tyr Ile Thr SerCys Glu Met Val Met Ala Pro Val His 610 615 620 Glu Ala Val Val Ser LeuHis Val Ser Lys Val Trp Asp Asp Ile Ser 625 630 635 640 Pro Gln Phe TyrAla Thr Phe Trp Ser Leu Thr Met Tyr Asp Leu Ala 645 650 655 Val Pro HisThr Ser Tyr Glu Arg Glu Val Asn Lys Leu Lys Val Gln 660 665 670 Met LysAla Ile Asp Asp Asn Gln Glu Met Pro Pro Asn Lys Lys Lys 675 680 685 LysGlu Lys Glu Arg Cys Thr Ala Leu Gln Asp Lys Leu Leu Glu Glu 690 695 700Glu Lys Lys Gln Met Glu His Val Gln Arg Val Leu Gln Arg Leu Lys 705 710715 720 Leu Glu Lys Asp Asn Trp Leu Leu Ala Lys Ser Thr Lys Asn Glu Thr725 730 735 Ile Thr Lys Phe Leu Gln Leu Cys Ile Phe Pro Arg Cys Ile PheSer 740 745 750 Ala Ile Asp Ala Val Tyr Cys Ala Arg Phe Val Glu Leu ValHis Gln 755 760 765 Gln Lys Thr Pro Asn Phe Ser Thr Leu Leu Cys Tyr AspArg Val Phe 770 775 780 Ser Asp Ile Ile Tyr Thr Val Ala Ser Cys Thr GluAsn Glu Ala Ser 785 790 795 800 Arg Tyr Gly Arg Phe Leu Cys Cys Met LeuGlu Thr Val Thr Arg Trp 805 810 815 His Ser Asp Arg Ala Thr Tyr Glu LysGlu Cys Gly Asn Tyr Pro Gly 820 825 830 Phe Leu Thr Ile Leu Arg Ala ThrGly Phe Asp Gly Gly Asn Lys Ala 835 840 845 Asp Gln Leu Asp Tyr Glu AsnPhe Arg His Val Val His Lys Trp His 850 855 860 Tyr Lys Leu Thr Lys AlaSer Val His Cys Leu Glu Thr Gly Glu Tyr 865 870 875 880 Thr His Ile ArgAsn Ile Leu Ile Val Leu Thr Lys Ile Leu Pro Trp 885 890 895 Tyr Pro LysVal Leu Asn Leu Gly Gln Ala Leu Glu Arg Arg Val His 900 905 910 Lys IleCys Gln Glu Glu Lys Glu Lys Arg Pro Asp Leu Tyr Ala Leu 915 920 925 AlaMet Gly Tyr Ser Gly Gln Leu Lys Ser Arg Lys Ser Tyr Met Ile 930 935 940Pro Glu Asn Glu Phe His His Lys Asp Pro Pro Pro Arg Asn Ala Val 945 950955 960 Ala Ser Val Gln Asn Gly Pro Gly Gly Gly Pro Ser Ser Ser Ser Ile965 970 975 Gly Ser Ala Ser Lys Ser Asp Glu Ser Ser Thr Glu Glu Thr AspLys 980 985 990 Ser Arg Glu Arg Ser Gln Cys Gly Val Lys Ala Val Asn LysAla Ser 995 1000 1005 Ser Thr Thr Pro Lys Gly Asn Ser Ser Asn Gly AsnSer Gly Ser 1010 1015 1020 Asn Ser Asn Lys Ala Val Lys Glu Asn Asp LysGlu Lys Gly Lys 1025 1030 1035 Glu Lys Glu Lys Glu Lys Lys Glu Lys ThrPro Ala Thr Thr Pro 1040 1045 1050 Glu Ala Arg Val Leu Gly Lys Asp GlyLys Glu Lys Pro Lys Glu 1055 1060 1065 Glu Arg Pro Asn Lys Asp Glu LysAla Arg Glu Thr Lys Glu Arg 1070 1075 1080 Thr Pro Lys Ser Asp Lys GluLys Glu Lys Phe Lys Lys Glu Glu 1085 1090 1095 Lys Ala Lys Asp Glu LysPhe Lys Thr Thr Val Pro Asn Ala Glu 1100 1105 1110 Ser Lys Ser Thr GlnGlu Arg Glu Arg Glu Lys Glu Pro Ser Arg 1115 1120 1125 Glu Arg Asp IleAla Lys Glu Met Lys Ser Lys Glu Asn Val Lys 1130 1135 1140 Gly Gly GluLys Thr Pro Val Ser Gly Ser Leu Lys Ser Pro Val 1145 1150 1155 Pro ArgSer Asp Ile Pro Glu Pro Glu Arg Glu Gln Lys Arg Arg 1160 1165 1170 LysIle Asp Thr His Pro Ser Pro Ser His Ser Ser Thr Val Lys 1175 1180 1185Asp Ser Leu Ile Glu Leu Lys Glu Ser Ser Ala Lys Leu Tyr Ile 1190 11951200 Asn His Thr Pro Pro Pro Leu Ser Lys Ser Lys Glu Arg Glu Met 12051210 1215 Asp Lys Lys Asp Leu Asp Lys Ser Arg Glu Arg Ser Arg Glu Arg1220 1225 1230 Glu Lys Lys Asp Glu Lys Asp Arg Lys Glu Arg Lys Arg AspHis 1235 1240 1245 Ser Asn Asn Asp Arg Glu Val Pro Pro Asp Leu Thr LysArg Arg 1250 1255 1260 Lys Glu Glu Asn Gly Thr Met Gly Val Ser Lys HisLys Ser Glu 1265 1270 1275 Ser Pro Cys Glu Ser Pro Tyr Pro Asn Glu LysAsp Lys Glu Lys 1280 1285 1290 Asn Lys Ser Lys Ser Ser Gly Lys Glu LysGly Ser Asp Ser Phe 1295 1300 1305 Lys Ser Glu Lys Met Asp Lys Ile SerSer Gly Gly Lys Lys Glu 1310 1315 1320 Ser Arg His Asp Lys Glu Lys IleGlu Lys Lys Glu Lys Arg Asp 1325 1330 1335 Ser Ser Gly Gly Lys Glu GluLys Lys His His Lys Ser Ser Asp 1340 1345 1350 Lys His Arg 1355 36 147PRT Homo sapiens 36 Met Ser Gly Glu Ala Thr Val Leu Ala Tyr His Ala ProGlu Glu Gln 1 5 10 15 Glu Gly Leu Leu Val Val Lys Val Glu Glu Glu AsnTyr Val Leu Asp 20 25 30 Gln Asp Phe Gly Leu Gln Glu Asn Pro Trp Ser GlnGlu Val Phe Arg 35 40 45 Gln Lys Phe Arg Gln Phe Ser Tyr Ser Asp Ser ThrGly Pro Arg Glu 50 55 60 Ala Leu Ser Arg Leu Arg Glu Leu Cys Cys Gln TrpLeu Arg Pro Glu 65 70 75 80 Val Cys Met Cys Ser Lys Glu Cys Met Ser IleLeu Glu Leu Leu Met 85 90 95 Leu Glu Gln Phe Leu Ala Ile Leu Pro Glu GluLeu Gln Ala Trp Leu 100 105 110 Arg Glu His Arg Gln Arg Met Glu Gly AsnCys Asp Tyr Ala Gly Gly 115 120 125 Ala Gly Lys Asn Trp Arg Ser Gln GlyThr Asp Ala Gly Lys Cys Ser 130 135 140 Gly Arg Lys 145 37 200 PRT Homosapiens 37 Met Ser Arg Arg Lys Gln Arg Lys Pro Gln Gln Leu Ile Ser AspCys 1 5 10 15 Glu Gly Pro Ser Ala Ser Glu Asn Gly Asp Ala Ser Glu GluAsp His 20 25 30 Pro Gln Val Cys Ala Lys Cys Cys Ala Gln Phe Thr Asp ProThr Glu 35 40 45 Phe Leu Ala His Gln Asn Ala Cys Ser Thr Asp Pro Pro ValMet Val 50 55 60 Ile Ile Gly Gly Gln Glu Asn Pro Asn Asn Ser Ser Ala SerSer Glu 65 70 75 80 Pro Arg Pro Glu Gly His Asn Asn Pro Gln Val Met AspThr Glu His 85 90 95 Ser Asn Pro Pro Asp Ser Gly Ser Ser Val Pro Thr AspPro Thr Trp 100 105 110 Gly Pro Glu Arg Arg Gly Glu Glu Ser Ser Gly HisPhe Leu Val Ala 115 120 125 Ala Thr Glu Pro Val Cys Gly Ile Pro Val LysTrp Pro Ala His Glu 130 135 140 Ala Leu Glu Phe Gln Leu His Leu His TyrHis Ser Lys Pro Gly Pro 145 150 155 160 Thr Ser Ala Val Trp Pro Arg AsnCys Gly Trp Glu Gly Ala Ser Asn 165 170 175 Asn Gly Ile Gln Gly Ser GlnGly Glu Asp Ser Pro Pro Pro Ile Ser 180 185 190 Ala Ser Cys Thr Gln GlySer Ala 195 200 38 1007 PRT Homo sapiens 38 Met Ser Arg Arg Lys Gln ArgLys Pro Gln Gln Leu Ile Ser Asp Cys 1 5 10 15 Glu Gly Pro Ser Ala SerGlu Asn Gly Asp Ala Ser Glu Glu Asp His 20 25 30 Pro Gln Val Cys Ala LysCys Cys Ala Gln Phe Thr Asp Pro Thr Glu 35 40 45 Phe Leu Ala His Gln AsnAla Cys Ser Thr Asp Pro Pro Val Met Val 50 55 60 Ile Ile Gly Gly Gln GluAsn Pro Asn Asn Ser Ser Ala Ser Ser Glu 65 70 75 80 Pro Arg Pro Glu GlyHis Asn Asn Pro Gln Val Met Asp Thr Glu His 85 90 95 Ser Asn Pro Pro AspSer Gly Ser Ser Val Pro Thr Asp Pro Thr Trp 100 105 110 Gly Pro Glu ArgArg Gly Glu Glu Ser Ser Gly His Phe Leu Val Ala 115 120 125 Ala Thr GlyThr Ala Ala Gly Gly Gly Gly Gly Leu Ile Leu Ala Ser 130 135 140 Pro LysLeu Gly Ala Thr Pro Leu Pro Pro Glu Ser Thr Pro Ala Pro 145 150 155 160Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Gly Val Gly Ser Gly His 165 170175 Leu Asn Ile Pro Leu Ile Leu Glu Glu Leu Arg Val Leu Gln Gln Arg 180185 190 Gln Ile His Gln Met Gln Met Thr Glu Gln Ile Cys Arg Gln Val Leu195 200 205 Leu Leu Gly Ser Leu Gly Gln Thr Val Gly Ala Pro Ala Ser ProSer 210 215 220 Glu Leu Pro Gly Thr Gly Thr Ala Ser Ser Thr Lys Pro LeuLeu Pro 225 230 235 240 Leu Phe Ser Pro Ile Lys Pro Val Gln Thr Ser LysThr Leu Ala Ser 245 250 255 Ser Ser Ser Ser Ser Ser Ser Ser Ser Gly AlaGlu Thr Pro Lys Gln 260 265 270 Ala Phe Phe His Leu Tyr His Pro Leu GlySer Gln His Pro Phe Ser 275 280 285 Ala Gly Gly Val Gly Arg Ser His LysPro Thr Pro Ala Pro Ser Pro 290 295 300 Ala Leu Pro Gly Ser Thr Asp GlnLeu Ile Ala Ser Pro His Leu Ala 305 310 315 320 Phe Pro Ser Thr Thr GlyLeu Leu Ala Ala Gln Cys Leu Gly Ala Ala 325 330 335 Arg Gly Leu Glu AlaThr Ala Ser Pro Gly Leu Leu Lys Pro Lys Asn 340 345 350 Gly Ser Gly GluLeu Ser Tyr Gly Glu Val Met Gly Pro Leu Glu Lys 355 360 365 Pro Gly GlyArg His Lys Cys Arg Phe Cys Ala Lys Val Phe Gly Ser 370 375 380 Asp SerAla Leu Gln Ile His Leu Arg Ser His Thr Gly Glu Arg Pro 385 390 395 400Tyr Lys Cys Asn Val Cys Gly Asn Arg Phe Thr Thr Arg Gly Asn Leu 405 410415 Lys Val His Phe His Arg His Arg Glu Lys Tyr Pro His Val Gln Met 420425 430 Asn Pro His Pro Val Pro Glu His Leu Asp Tyr Val Ile Thr Ser Ser435 440 445 Gly Leu Pro Tyr Gly Met Ser Val Pro Pro Glu Lys Ala Glu GluGlu 450 455 460 Ala Ala Thr Pro Gly Gly Gly Val Glu Arg Lys Pro Leu ValAla Ser 465 470 475 480 Thr Thr Ala Leu Ser Ala Thr Glu Ser Leu Thr LeuLeu Ser Thr Ser 485 490 495 Ala Gly Thr Ala Thr Ala Pro Gly Leu Pro AlaPhe Asn Lys Phe Val 500 505 510 Leu Met Lys Ala Val Glu Pro Lys Asn LysAla Asp Glu Asn Thr Pro 515 520 525 Pro Gly Ser Glu Gly Ser Ala Ile SerGly Val Ala Glu Ser Ser Thr 530 535 540 Ala Thr Arg Met Gln Leu Ser LysLeu Val Thr Ser Leu Pro Ser Trp 545 550 555 560 Ala Leu Leu Thr Asn HisPhe Lys Ser Thr Gly Ser Phe Pro Phe Pro 565 570 575 Tyr Val Leu Glu ProLeu Gly Ala Ser Pro Ser Glu Thr Ser Lys Leu 580 585 590 Gln Gln Leu ValGlu Lys Ile Asp Arg Gln Gly Ala Val Ala Val Thr 595 600 605 Ser Ala AlaSer Gly Ala Pro Thr Thr Ser Ala Pro Ala Pro Ser Ser 610 615 620 Ser AlaSer Ser Gly Pro Asn Gln Cys Val Ile Cys Leu Arg Val Leu 625 630 635 640Ser Cys Pro Arg Ala Leu Arg Leu His Tyr Gly Gln His Gly Gly Glu 645 650655 Arg Pro Phe Lys Cys Lys Val Cys Gly Arg Ala Phe Ser Thr Arg Gly 660665 670 Asn Leu Arg Ala His Phe Val Gly His Lys Ala Ser Pro Ala Ala Arg675 680 685 Ala Gln Asn Ser Cys Pro Ile Cys Gln Lys Lys Phe Thr Asn AlaVal 690 695 700 Thr Leu Gln Gln His Val Arg Met His Leu Gly Gly Gln IlePro Asn 705 710 715 720 Gly Gly Thr Ala Leu Pro Glu Gly Gly Gly Ala AlaGln Glu Asn Gly 725 730 735 Ser Glu Gln Ser Thr Val Ser Gly Ala Gly SerPhe Pro Gln Gln Gln 740 745 750 Ser Gln Gln Pro Ser Pro Glu Glu Glu LeuSer Glu Glu Glu Glu Glu 755 760 765 Glu Asp Glu Glu Glu Glu Glu Asp ValThr Asp Glu Asp Ser Leu Ala 770 775 780 Gly Arg Gly Ser Glu Ser Gly GlyGlu Lys Ala Ile Ser Val Arg Gly 785 790 795 800 Asp Ser Glu Glu Ala SerGly Ala Glu Glu Glu Val Gly Thr Val Ala 805 810 815 Ala Ala Ala Thr AlaGly Lys Glu Met Asp Ser Asn Glu Lys Thr Thr 820 825 830 Gln Gln Ser SerLeu Pro Pro Pro Pro Pro Pro Asp Ser Leu Asp Gln 835 840 845 Pro Gln ProMet Glu Gln Gly Ser Ser Gly Val Leu Gly Gly Lys Glu 850 855 860 Glu GlyGly Lys Pro Glu Arg Ser Ser Ser Pro Ala Ser Ala Leu Thr 865 870 875 880Pro Glu Gly Glu Ala Thr Ser Val Thr Leu Val Glu Glu Leu Ser Leu 885 890895 Gln Glu Ala Met Arg Lys Glu Pro Gly Glu Ser Ser Ser Arg Lys Ala 900905 910 Cys Glu Val Cys Gly Gln Ala Phe Pro Ser Gln Ala Ala Leu Glu Glu915 920 925 His Gln Lys Thr His Pro Lys Glu Gly Pro Leu Phe Thr Cys ValPhe 930 935 940 Cys Arg Gln Gly Phe Leu Glu Arg Ala Thr Leu Lys Lys HisMet Leu 945 950 955 960 Leu Ala His His Gln Val Gln Pro Phe Ala Pro HisGly Pro Gln Asn 965 970 975 Ile Ala Ala Leu Ser Leu Val Pro Gly Cys SerPro Ser Ile Thr Ser 980 985 990 Thr Gly Leu Ser Pro Phe Pro Arg Lys AspAsp Pro Thr Ile Pro 995 1000 1005 39 572 PRT Homo sapiens 39 Met Gly LysLys Leu Asp Leu Ser Lys Leu Thr Asp Glu Glu Ala Gln 1 5 10 15 His ValLeu Glu Val Val Gln Arg Asp Phe Asp Leu Arg Arg Lys Glu 20 25 30 Glu GluArg Leu Glu Ala Leu Lys Gly Lys Ile Lys Lys Glu Ser Ser 35 40 45 Lys ArgGlu Leu Leu Ser Asp Thr Ala His Leu Asn Glu Thr His Cys 50 55 60 Ala ArgCys Leu Gln Pro Tyr Gln Leu Leu Val Asn Ser Lys Arg Gln 65 70 75 80 CysLeu Glu Cys Gly Leu Phe Thr Cys Lys Ser Cys Gly Arg Val His 85 90 95 ProGlu Glu Gln Gly Trp Ile Cys Asp Pro Cys His Pro Ala Arg Val 100 105 110Val Lys Ile Gly Ser Leu Glu Trp Tyr Tyr Glu His Val Lys Ala Arg 115 120125 Phe Lys Arg Phe Gly Ser Ala Lys Val Ile Arg Ser Leu His Gly Arg 130135 140 Leu Gln Gly Gly Ala Gly Pro Glu Leu Ile Ser Glu Glu Arg Ser Gly145 150 155 160 Asp Ser Asp Gln Thr Asp Glu Asp Gly Glu Pro Gly Ser GluAla Gln 165 170 175 Ala Gln Ala Gln Pro Phe Gly Ser Lys Lys Lys Arg LeuLeu Ser Val 180 185 190 His Asp Phe Asp Phe Glu Gly Asp Ser Asp Asp SerThr Gln Pro Gln 195 200 205 Gly His Ser Leu His Leu Ser Ser Val Pro GluAla Arg Asp Ser Pro 210 215 220 Gln Ser Leu Thr Asp Glu Ser Cys Ser GluLys Ala Ala Pro His Lys 225 230 235 240 Ala Glu Gly Leu Glu Glu Ala AspThr Gly Ala Ser Gly Cys His Ser 245 250 255 His Pro Glu Glu Gln Pro ThrSer Ile Ser Pro Ser Arg His Gly Ala 260 265 270 Leu Ala Glu Leu Cys ProPro Gly Gly Ser His Arg Met Ala Leu Gly 275 280 285 Thr Ala Ala Ala LeuGly Ser Asn Val Ile Arg Asn Glu Gln Leu Pro 290 295 300 Leu Gln Tyr LeuAla Asp Val Asp Thr Ser Asp Glu Glu Ser Ile Arg 305 310 315 320 Ala HisVal Met Ala Ser His His Ser Lys Arg Arg Gly Arg Ala Ser 325 330 335 SerGlu Ser Gln Gly Leu Gly Ala Gly Ala Arg Thr Glu Ala Asp Val 340 345 350Glu Glu Glu Ala Leu Arg Arg Lys Leu Glu Glu Leu Thr Ser Asn Val 355 360365 Ser Asp Gln Glu Thr Ser Ser Glu Glu Glu Glu Ala Lys Asp Glu Lys 370375 380 Ala Glu Pro Asn Arg Asp Lys Ser Val Gly Pro Leu Pro Gln Ala Asp385 390 395 400 Pro Glu Val Gly Thr Ala Ala His Gln Thr Asn Arg Gln GluLys Ser 405 410 415 Pro Gln Asp Pro Gly Asp Pro Val Gln Tyr Asn Arg ThrThr Asp Glu 420 425 430 Glu Leu Ser Glu Leu Glu Asp Arg Val Ala Val ThrAla Ser Glu Val 435 440 445 Gln Gln Ala Glu Ser Glu Val Ser Asp Ile GluSer Arg Ile Ala Ala 450 455 460 Leu Arg Ala Ala Gly Leu Thr Val Lys ProSer Gly Lys Pro Arg Arg 465 470 475 480 Lys Ser Asn Leu Pro Ile Phe LeuPro Arg Val Ala Gly Lys Leu Gly 485 490 495 Lys Arg Pro Glu Asp Pro AsnAla Asp Pro Ser Ser Glu Ala Lys Ala 500 505 510 Met Ala Val Pro Tyr LeuLeu Arg Arg Lys Phe Ser Asn Ser Leu Lys 515 520 525 Ser Gln Gly Lys AspAsp Asp Ser Phe Asp Arg Lys Ser Val Tyr Arg 530 535 540 Gly Ser Leu ThrArg Arg Asn Pro Asn Ala Arg Lys Gly Met Ala Ser 545 550 555 560 His ThrPhe Ala Lys Pro Val Val Ala His Gln Ser 565 570

1. An isolated polynucleotide comprising, a polynucleotide sequencewhich codes without interruption for a differentially-regulated humanprostate cancer polypeptide having an amino acid sequence selected fromSEQ ID NO 2, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, or 31, ora complement thereto.
 2. An isolated polynucleotide of claim 1,comprising a polynucleotide sequence selected from SEQ ID NO 1, 3, 4, 6,8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and
 30. 3. An isolatedpolynucleotide comprising, a polynucleotide sequence which codes withoutinterruption for a differentially-regulated human prostate cancerpolypeptide, said polynucleotide sequence having 90% or more nucleotidesequence identity along its entire length to a polynucleotide sequenceselected from: SEQ ID NO 1, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24,26, 28, and 30, or a complement thereto.
 4. An isolated polynucleotidecomprising, a polynucleotide sequence which is specific for adifferentially-regulated human prostate cancer gene of claim
 1. 5. Anisolated polynucleotide of claim 4, wherein said polynucleotide iseffective in a polymerase chain reaction.
 6. An isolateddifferentially-regulated human prostate cancer polypeptide having anamino acid sequence selected from SEQ ID NO 2, 5, 7, 9, 11, 13, 15, 17,19, 21, 23, 25, 27, 29, or
 31. 7. An isolated differentially-regulatedhuman prostate polypeptide having 90% or more amino acid sequenceidentity along its entire length to an amino acid sequence selected fromSEQ ID NO 2, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, or
 31. 8.A method of detecting a nucleic acid coding for adifferentially-regulated human prostate cancer gene, comprising,contacting a sample comprising nucleic acid with a polynucleotide probespecific for a differentially-regulated human prostate cancer gene ofclaim 1 under conditions effective for said probe to hybridizespecifically with said gene, and detecting hybridization between saidprobe and said nucleic acid.
 9. A method of claim 8, wherein saiddetecting is performed by: Northern blot analysis, polymerase chainreaction (PCR), reverse transcriptase PCR, RACE PCR, or in situhybridization.
 10. A method of treating a prostate cancer showingelevated expression of a differentially-regulated human prostate cancergene, comprising: administering to a subject in need thereof atherapeutic agent which is effective for regulating expression of adifferentially-regulated human prostate cancer gene polynucleotide, orpolypeptide encoded thereby, of claim
 1. 11. A method for identifying anagent that modulates the expression of a differentially-regulated humanprostate cancer gene in cells expressing said gene, or the biologicalactivity of a polypeptide encoded thereby, comprising, contacting a cellwith a test agent under conditions effective for said test agent tomodulate the expression of a human gene of claim 1, or the biologicalactivity of a polypeptide encoded thereby, in said cells, anddetermining whether said test agent modulates said gene or polypeptide.12. A method of claim 11, wherein said agent is an antisensepolynucleotide to said gene, and which is effective to inhibit itstranslation.
 13. A method of detecting polymorphisms in adifferentially-regulated human prostate cancer gene, comprising,comparing the structure of: genomic DNA comprising all or part of ahuman differentially-regulated prostate cancer gene, mRNA comprising allor part of a human differentially-regulated prostate cancer gene, cDNAcomprising all or part of a human differentially-regulated prostatecancer gene, or a polypeptide comprising all or part of a humandifferentially-regulated prostate cancer gene, with the completestructure of a human differentially-regulated prostate cancer gene ofclaim
 2. 14. A method of claim 13, wherein said polymorphism is anucleotide deletion, substitution, inversion, or transposition.
 15. Amammalian cell whose genome comprises a functional disruption of adifferentially-regulated human prostate cancer gene of claim 2 within anucleotide sequence which is specific for said gene.
 16. A non-human,transgenic mammal comprising a cell of claim 15, said mammal beingsusceptible to prostate cancer.
 17. An antibody which is specific-for: apolypeptide sequence which is specific for a humandifferentially-regulated prostate cancer gene of claim
 1. 18. A methodof selecting a human differentially-regulated prostate cancer genepolynucleotide or amino acid sequence from a database, comprising:displaying, in a computer-readable medium, a polynucleotide sequence orpolypeptide sequence for a human differentially-regulated prostatecancer gene of claim 2, or complements to the polynucleotides sequence,wherein said displayed sequences have been retrieved from said databaseupon selection by a user.